Patent Publication Number: US-9410208-B2

Title: Marker and reagent for detection of human IL-17-producing helper T cells, and method for detection of human IL-17-producing helper T cells

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     This is a divisional of U.S. patent application Ser. No. 13/360,324, filed Jan. 27, 2012, which is a continuation of International Application PCT/JP2010/062807 filed Jul. 29, 2010, which claims benefit of JP 2009-176755, filed Jul. 29, 2009, all of which are incorporated herein by reference in their entirety. 
    
    
     BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     The present invention relates to a marker and reagent for detecting human IL-17-producing helper T-cells (hereinafter also referred to as “Th17 cells”) and a method for detecting human Th17 cells. 
     2. Description of the Related Art 
     Rheumatoid arthritis (hereinafter referred to as “RA”) is the systemic inflammatory autoimmune disease whose main clinical symptom is arthritis. The state of RA is diagnosed by rational symptoms such as joint pain or by visual procedures such as the observations on the extent of swelling or bone X-ray. However, no quantitative index has been established. Thus, no quantitative method for continuously monitoring the treatment effects has been established under the current state of the art. 
     The pathogenesis of RA has not been elucidated. It is considered that bacterial infections and the like trigger an inflammation in joint tissues via complicated networks of immunocytes and cytokines. 
     Helper T-cells play a central role in immune reactions. Immature helper T-cells (naïve T-cells) are differentiated into helper T-cells when an antigen is presented by antigen-presenting cells. When specific cytokines are present at this time, naïve T-cells are differentiated into four types of the cells, which are helper T-cells producing interferon (IFN)-γ (Th1 cells), helper T-cells producing interleukin (IL)-4 (Th2 cells), helper T-cells producing IL-17 (Th17 cells) and regulatory T-cells having immunosuppressive effects (Treg cells). 
     It has been shown that among these helper T-cells, Th17 cells can be involved in the onset of RA. 
     It has been suggested that IL-17 is deeply involved in the formation of pathological conditions and in particular joint and bone deformities because the level of IL-17 is significantly higher in synovial fluid of RA patients than in that of the patients of osteoarthritis and T-cells in synovial tissue from RA patients include IL-17 positive cells (see Japanese Unexamined Patent Publication No. 2000-186046). Japanese Unexamined Patent Publication No. 2000-186046 also discloses that IL-17 can be used as a diagnostic marker of RA. 
     Japanese Unexamined Patent Publication No. 2007-506100 discloses that the analysis of cytokines in peripheral blood serum of RA patients revealed that the levels of IFN-γ, IL-1β, TNF-α, G-CSF, GM-CSF, IL-6, IL-4, IL-10, IL-13, IL-5 and IL-7 were significantly high and the levels of IL-2, CXCL8/IL-8, IL-12 and CCL2/MCP-1 were not high in RA patients. 
     According to the studies by Ivanov et al. (“The Orphan Nuclear Receptor RORγt Directs the Differentiation Program of Proinflammatory IL-17+ T Helper Cells”, Cell, 2006, 126, p. 1121-1133), Stumhofer et al. (“Interleukin 27 negatively regulates the development of interleukin 17-producing T helper cells during chronic inflammation of the central nervous system”, Nature Immunology, 2006, vol. 7, p. 937-945), and Wilson et al. (“Development, cytokine profile and function of human interleukin 17-producing helper T cells”, Nature Immunology, 2007, vol. 8, p. 950-95′7), the following facts have been shown about Th17 cells:
         a nuclear receptor called RORγt has an important role in the differentiation of Th17 cells;   IL-6, IL-23 and TGF-β induce the differentiation of immature helper T-cells (naïve T-cells) to Th17 cells;   they express IL-17A, IL-17F, IL-6, IL-22, IL-26, TNF, IFN-γ and CCL20; and   IL-23 receptor and IL-12 receptor β are located on the surface of Th17 cells.       

     SUMMARY OF THE INVENTION 
     In the above documents by Ivanov et al., Stumhofer et al. and Wilson et al., the amount of IL-17 is measured by enzyme linked immunosorbent assay (ELISA) using antibodies specific to IL-17. 
     The relations between Th17 cells and autoimmune diseases, preferably RA may be more deeply understood by establishing a method which allows not only measurement of the amount of IL-17 but also detection of Th17 cells per se. 
     The present inventors aimed to find molecular markers that allows specific detection of human Th17 cells. 
     The present inventors isolated Th17 cells from peripheral blood of a healthy adult and identified the genes which are specifically expressed in the obtained Th17 cells, thereby completing the present invention. 
     Thus, the present invention provides a polynucleotide marker for detecting human Th17 cells which is a polynucleotide having a nucleic acid sequence of at least one gene selected from the group consisting of:
         genes encoding membrane proteins consisting of: ADAM12 (ADAM metallopeptidase domain 12), ANKS1B (ankyrin repeat and sterile alpha motif domain containing 1B), ATP6V0A4 (ATPase, H+ transporting, lysosomal V0 subunit a4), ATP9A (ATPase, class II, type 9A), BVES (blood vessel epicardial substance), C5orf40 (chromosome 5 open reading frame 40), CDH4 (cadherin 4, type 1, R-cadherin (retinal)), DIO2 (deiodinase, iodothyronine, type II), DMD (dystrophin), GPR34 (G protein-coupled receptor 34), IRS2 (insulin receptor substrate 2), KCNE3 (potassium voltage-gated channel, Isk-related family, member 3), L1CAM (L1 cell adhesion molecule), MCAM (melanoma cell adhesion molecule), MFAP3L (microfibrillar-associated protein 3-like), MYO7A (myosin VIIA), PTPRM (protein tyrosine phosphatase, receptor type, M), SHROOM2 (shroom family member 2), SLC16A4 (solute carrier family 16, member 4 (monocarboxylic acid transporter 5)), SLCO2B1 (solute carrier organic anion transporter family, member 2B1), TANC2 (tetratricopeptide repeat, ankyrin repeat and coiled-coil containing 2), TJP1 (tight junction protein 1 (zona occludens 1)), TMEM163 (transmembrane protein 163), TNS3 (tensin 3), UPK1B (uroplakin 1B), WDFY3 (WD repeat and FYVE domain containing 3), DRD2 (dopamine receptor D2), GJC1 (gap junction protein, gamma 1, 45 kDa), PGBD5 (LOC100134440) (piggyBac transposable element derived 5 (similar to PGBD5 protein)), MS4A 7 (membrane-spanning 4-domains, subfamily A, member 7), ODZ4 (odz, odd Oz/ten-m homolog 4), PHKA1 (phosphorylase kinase, alpha 1), RGS1 (regulator of G-protein signaling 1), SHB (Src homology 2 domain containing adaptor protein B), SLC44A3 (solute carrier family 44, member 3), SLC6A15 (solute carrier family 6 (neutral amino acid transporter), member 15), SYNGR3 (synaptogyrin 3), AKAP12 (A kinase (PRKA) anchor protein 12), C9orf125 (chromosome 9 open reading frame 125), DPY19L2 (dpy-19-like 2), HRH4 (histamine receptor H4), MUC20 (mucin 20, cell surface associated), POPDC3 (popeye domain containing 3), SORBS1 (sorbin and SH3 domain containing 1), TANC1 (tetratricopeptide repeat, ankyrin repeat and coiled-coil containing 1), TMEM44 (transmembrane protein 44) and UNC13C (unc-13 homolog C);       

     genes encoding secretory proteins consisting of: CXCL13 (chemokine (C—X—C motif) ligand 13), PCOLCE2 (procollagen C-endopeptidase enhancer 2), PNOC (prepronociceptin), SMPDL3A (sphingomyelin phosphodiesterase, acid-like 3A), TGFBI (transforming growth factor, beta-induced), C17orf99 (chromosome 17 open reading frame 99), EBI3 (Epstein-Barr virus induced 3), IL1A (interleukin 1, alpha) and WNT3 (wingless-type MMTV integration site family, member 3); 
     genes encoding intracellular proteins consisting of: BCAT1 (branched chain aminotransferase 1, cytosolic), BHLHE22 (basic helix-loop-helix family, member e22), C13orf18 (LOC728970) (chromosome 13 open reading frame 18 (hypothetical LOC728970)), CA2 (carbonic anhydrase II), CCDC3 (coiled-coil domain containing 3), CDS1 (CDP-diacylglycerol synthase (phosphatidate cytidylyltransferase) 1), CHN1 (chimerin (chimaerin) 1), CLIC5 (LOC100131610) (chloride intracellular channel 5 (similar to chloride intracellular channel 5)), CTSH (cathepsin H), CYP7B1 (cytochrome P450, family 7, subfamily B, polypeptide 1), DAPK2 (death-associated protein kinase 2), DMRT1 (doublesex and mab-3 related transcription factor 1), DSE (dermatan sulfate epimerase), FBXL17 (F-box and leucine-rich repeat protein 17), FBXL21 (F-box and leucine-rich repeat protein 21), FHOD3 (formin homology 2 domain containing 3), H2AFY2 (H2A histone family, member Y2), HLX (H2.0-like homeobox), IRAK3 (interleukin-1 receptor-associated kinase 3), MACC1 (metastasis associated in colon cancer 1), MAML3 (mastermind-like 3), MYO10 (myosin X), OTUB2 (OTU domain, ubiquitin aldehyde binding 2), PAPSS2 (3′-phosphoadenosine 5′-phosphosulfate synthase 2), PCBP3 (Poly (rC) binding protein 3 (PCBP3), transcript variant 2), PDE4DIP (phosphodiesterase 4D interacting protein), PLD1 (phospholipase D1, phosphatidylcholine-specific), PPARG (peroxisome proliferator-activated receptor gamma), PTPN13 (Protein tyrosine phosphatase, non-receptor type 13 (APO-1/CD95 (Fas)-associated phosphatase)), RGS18 (regulator of G-protein signaling 18), SIM1 (single-minded homolog 1), SNAI2 (snail homolog 2), SOX2 (SRY (sex determining region Y)-box 2), SPIRE1 (spire homolog 1), TBC1D12 (TBC1 domain family, member 12), TGM5 (transglutaminase 5), TMOD1 (tropomodulin 1), TUBB6 (tubulin, beta 6), DDIT4L (DNA-damage-inducible transcript 4-like), DHRS9 (dehydrogenase/reductase (SDR family) member 9), ERC2 (ELKS/RAB6-interacting/CAST family member 2), FERMT2 (fermitin family homolog 2), HHEX (hematopoietically expressed homeobox), HS3ST1 (heparan sulfate (glucosamine) 3-O-sulfotransferase 1), NR5A2 (nuclear receptor subfamily 5, group A, member 2), PHLDA1 (pleckstrin homology-like domain, family A, member 1), RBM20 (RNA binding motif protein 20), NINL (ninein-like), RTN2 (reticulon 2), SH3RF2 (SH3 domain containing ring finger 2), TSHZ2 (teashirt zinc finger homeobox 2), EML1 (echinoderm microtubule associated protein like 1), HIST1H2BC (histone cluster 1, H2bc), MAP3K4 (mitogen-activated protein kinase kinase kinase 4), PDK4 (pyruvate dehydrogenase kinase, isozyme 4), RGS2 (regulator of G-protein signaling 2) and RGS20 (regulator of G-protein signaling 20); 
     genes consisting of: C1orf106 (chromosome 1 open reading frame 106), C6orf145 (chromosome 6 open reading frame 145), LOC401097 (Similar to LOC166075), MAMLD1 (mastermind-like domain containing 1), ZC3H12C (zinc finger CCCH-type containing 12C), C12orf64 (chromosome 12 open reading frame 64), C6orf168 (chromosome 6 open reading frame 168), CAMSAP1L1 (calmodulin regulated spectrin-associated protein 1-like 1) and MAGED4 (MAGED4B) (melanoma antigen family D, 4, (melanoma antigen family D, 4B)); and
         genes comprising at least one nucleic acid sequence selected from SEQ ID NOs:147 to 151, 157 to 162 and 167 to 174;   or a variant and fragment thereof.       

     The present invention also provides a protein marker for detecting human Th17 cells which is a protein encoded by at least one of the above genes or a functionally equivalent variant and fragment thereof. 
     The present invention further provides a method for detecting human Th17 cells comprising detecting the presence of at least one polynucleotide marker for detecting human Th17 cells or at least one protein marker for detecting human Th17 cells in a sample containing cells derived from human. 
     In addition, the present invention provides a reagent for detecting human Th17 cells comprising at least one substance selected from a nucleic acid probe which specifically hybridizes to the above polynucleotide marker; and a nucleic acid aptamer, antibody, ligand or receptor which specifically binds to the above protein marker. 
     Human Th17 cells can be specifically detected by detecting at least one polynucleotide marker or protein marker for detecting human Th17 cells of the present invention. It may also allow detection of the possibility that a patient has a disease in which Th17 cells may be involved such as autoimmune diseases, e.g. RA. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  shows graphs of the expression levels of the genes which are known to be specifically expressed in Th17 cells (IL23R, IL17A, IL17F, IL22, IL26 and RORC) in Th1, Th2, Treg and Th17 cells; 
         FIG. 2  shows histograms of fluorescent intensity obtained by the analysis of MCAM measurement samples; 
         FIG. 3  shows histograms of fluorescent intensity obtained by the analysis of PTPRM measurement samples; 
         FIG. 4  shows histograms of fluorescent intensity obtained by the analysis of GPR34 measurement samples; 
         FIG. 5  shows histograms of fluorescent intensity obtained by the analysis of CCR6 measurement samples; 
         FIG. 6  shows histograms of fluorescent intensity obtained by the analysis of IL-17A measurement samples; 
         FIG. 7  shows histograms of fluorescent intensity obtained by the analysis of IFN-γ measurement samples; 
         FIG. 8  shows histograms of fluorescent intensity obtained by the analysis of IL-4 measurement samples; and 
         FIG. 9  shows histograms of fluorescent intensity obtained by the analysis of FOXP3 measurement samples. 
     
    
    
     DETAILED DESCRIPTION OF THE EMBODIMENTS 
     The polynucleotide marker for detecting human Th17 cells of the present invention is the polynucleotide having a nucleic acid sequence of at least one gene selected from the group consisting of the above genes, or a variant and fragment thereof. 
     Preferably, the polynucleotide has a nucleic acid sequence of at least one gene selected from the group consisting of:
         genes encoding membrane proteins consisting of: ADAM12, ATP6V0A4, ATP9A, BVES, C5orf40, CDH4, DIO2, GPR34, L1CAM, MCAM, PTPRM, SHROOM2, TMEM163, UPK1B, DRD2, PGBD5 (LOC100134440), ODZ4, SLC6A15, AKAP12, C9orf125, POPDC3 and UNC13C;   genes encoding secretory proteins consisting of: PCOLCE2, PNOC, TGFBI and IL1A; and       

     genes encoding intracellular proteins consisting of: BHLHE22, PPARG, SIM1 and SNAI2. 
     The present polynucleotide marker for detecting human Th17 cells is the polynucleotide, variant or fragment thereof which has been found to be specifically present in Th17 cells rather than in other helper T-cells derived from human peripheral blood (Th1, Th2 and Treg cells). 
     Therefore, by detecting at least one of the above polynucleotide markers, Th17 cells can be distinguished from Th1, Th2 and Treg cells and specifically identified, and an index for activity of diseases in vivo can be studied in which Th17 cells may be involved. 
     As used herein, the term “gene” has the same meaning as that is commonly recognized in the art, and refers to a part of a genome which is transcribed into mRNA and translated into a protein. 
     In the present specification, genes containing at least one nucleic acid sequence selected from SEQ ID NOs: 147 to 151, 157 to 162 and 167 to 174 are the genes to be transcribed into mRNAs containing at least one of these nucleic acid sequences or a complementary sequence thereof. Thus, genes containing at least one nucleic acid sequence selected from SEQ ID NOs: 147 to 151, 157 to 162 and 167 to 174 comprise genes containing a nucleic acid sequence complementary to at least one nucleic acid sequence selected from SEQ ID NOs: 147 to 151, 157 to 162 and 167 to 174. 
     As used herein, a membrane protein means a protein existing in a cell membrane and being contained in a membrane fraction of cells. A secretory protein means a protein synthesized in cells and secreted to the outside of the cell membrane. An intracellular protein means a protein which is mainly present in cells. 
     As used herein, the phrase that a polynucleotide is “specifically expressed” in Th17 cells means that the expression level of the polynucleotide in Th17 cells is significantly higher than the expression level of the polynucleotide in cells other than Th17 cells. 
     Specifically, it means that the expression level of the polynucleotide in Th17 cells is about two times or more of the expression level of the polynucleotide in cells other than Th17 cells. Preferably, the expression level of the polynucleotide in Th17 cells is about two times or more of the expression level of the polynucleotide in helper T-cells other than Th17 cells (Th1, Th2 and Treg cells). 
     The nucleotide sequences of the present polynucleotide markers are already known. They can be obtained from, for example, Unigene (a database provided by National Center for Biotechnology Information (NCBI) of National Library of Medicine). Unigene codes for the nucleic acid sequences of the present polynucleotide markers are specified in Table 9. 
     As used herein, “variant” of a polynucleotide means a polynucleotide into which a mutation has been introduced that does not alter the nature of the protein encoded by the above gene. Such mutation includes a deletion, substitution or addition of one or more nucleotides to the nucleic acid sequence of the above gene. 
     As used herein, “fragment” of a polynucleotide means a polynucleotide having a contiguous part of the nucleic acid sequence of the above gene and having a length which allows its specific hybridization with a nucleic acid probe for detecting human Th17 cells described hereinafter. 
     The variant of the polynucleotide as the present polynucleotide marker for detecting human Th17 cells has generally at least 80%, more preferably at least 85%, further preferably at least 90% and particularly preferably at least 95% homology with the nucleic acid sequence of the above gene. 
     As used herein, the homology of nucleic acid and amino acid sequences is calculated in BLASTN, BLASTP, BLASTX or TBLASTN (e.g. available from http://www.ncbi.nlm.nih.gov) with default settings. 
     The polynucleotide marker may be any of DNA or RNA, and may be the gene per se (DNA), mRNA, cDNA or cRNA. 
     Human Th17 cells can also be detected by detecting at least one protein encoded by the above gene. Thus, the present invention also provides the protein marker for detecting human Th17 cells consisting of the protein encoded by at least one of the above genes or a functionally equivalent variant and fragment thereof. 
     Preferably, the above protein is encoded by at least one gene selected from the group consisting of:
         genes encoding membrane proteins consisting of: ADAM12, ATP6V0A4, ATP9A, BVES, C5orf40, CDH4, DIO2, GPR34, L1CAM, MCAM, PTPRM, SHROOM2, TMEM163, UPK1B, DRD2, PGBD5 (LOC100134440), ODZ4, SLC6A15, AKAP12, C9orf125, POPDC3 and UNC13C;   genes encoding secretory proteins consisting of: PCOLCE2, PNOC, TGFBI and IL1A; and   genes encoding intracellular proteins consisting of: BHLHE22, PPARG, SIM1 and SNAI2.       

     More preferably, the above protein is a membrane protein encoded by at least one gene selected from the group consisting of GPR34, MCAM and PTPRM. 
     The amino acid sequence of such protein marker can be obtained based on the nucleic acid sequence of the polynucleotide marker obtained from Unigene and the like. It can also be obtained from databases provided by NCBI and the like. NCBI code numbers for the amino acid sequences of the present protein markers for detecting human Th17 cells are specified in Table 9. 
     The protein marker for detecting human Th17 cells is the protein encoded by the above gene, a functionally equivalent variant or fragment thereof. 
     As used herein, “functionally equivalent variant” of a protein means a protein into which a mutation has been introduced that does not alter functions of the protein. Such mutation includes a deletion, substitution or addition of one or more amino acids to the known amino acid sequence of the protein. 
     As used herein, “fragment” of a protein means a protein having a contiguous amino acid sequence of the protein encoded by the above gene or a functionally equivalent variant thereof and being able to specifically bind to a nucleic acid aptamer, antibody, ligand or receptor for detecting human Th17 cells described hereinafter. 
     The functionally equivalent variant of the protein corresponding to the present protein marker for detecting human Th17 cells has generally at least 80%, preferably at least 85%, more preferably at least about 90% and particularly preferably at least 95% homology with the known amino acid sequence of the protein encoded by the above gene. 
     A molecule that can specifically hybridize to the present polynucleotide marker can be used for detection of the marker, making it useful as a probe for detecting human Th17 cells. The probe may be a nucleic acid probe such as DNA or RNA, or a peptide probe that can specifically hybridize to the polynucleotide marker. The probe for detecting human Th17 cells is preferably a nucleic acid probe, particularly a DNA probe for detecting the polynucleotide marker. 
     As used herein, the phrase “can specifically hybridize” means that it can hybridize to a target nucleic acid molecule (the polynucleotide marker) under a stringent condition. 
     As used herein, “stringent condition” means a condition under which the probe for detecting human Th17 cells can hybridize to the target polynucleotide marker with a detectably higher extent than it does to a polynucleotide other than the target polynucleotide marker (e.g. more than at least two times of the background). 
     The stringent condition generally depends on the sequences and varies depending on various circumstances. Generally, the stringent condition is selected so that it is about 5° C. lower than a thermal melting point of the specific sequence under a certain ionic strength and pH. This Tm is a temperature at which 50% of the complementary probe hybridizes to the target sequence in equilibrium (under a certain ionic strength, pH and nucleic acid composition). 
     Such condition may be those which are used in conventional hybridization techniques between polynucleotides such as PCR, microarray or Southern blotting. 
     Specifically, it may be a condition of pH 7.0 to 9.0, a salt concentration of lower than about 1.5M Na-ion, more specifically about 0.01 to 1.0 M Na-ion concentration (or other salt) and a temperature of at least about 30° C. More specifically, the stringent condition in microarray technique includes the hybridization at 37° C. in 50% formamide, 1M NaCl and 1% SDS and washing at 60 to 65° C. in 0.1×SSC. 
     The stringent condition in PCR technique includes a condition of pH 7 to 9, 0.01 to 0.1 M Tris-HCl, 0.05 to 0.15 M potassium ion concentration (or other salt) and at least about 55° C. 
     The sequence of the nucleic acid probe for detecting human Th17 cells can be appropriately selected by a person skilled in the art based on the common technical knowledge in the art and the sequence of the polynucleotide marker so that it can specifically hybridize to the polynucleotide marker. 
     The nucleic acid probe for detecting human Th17 cells can be designed by using, for example, a commonly available primer designing software (e.g. Primer3 (available from frodo.wi.mit.edu/cgi-bin/primer3/primer3.cgi) or DNASIS Pro (Hitachi Software Engineering Co., Ltd.)). 
     The nucleic acid probe for detecting human Th17 cells can be prepared according to polynucleotide synthesis methods which are well-known in the art. 
     The nucleic acid probe for detecting human Th17 cells may be labeled with a labeling substance normally used in the art. The labeled nucleic acid probe allows an easy detection of the polynucleotide marker for detecting human Th17 cells, namely of human Th17 cells. 
     The labeling substance may be a labeling substance generally used in the art including radioisotopes such as  32 P, fluorescent substances such as fluorescein, enzymes such as alkaline phosphatase and horseradish peroxidase, and biotin. 
     Human Th17 cells can be specifically detected by using one or more nucleic acid probes for detecting human Th17 cells. For example, a DNA chip or microarray for detecting the polynucleotide marker for detecting human Th17 cells can be obtained by immobilizing one or more probes on a substrate according to a method well-known in the art. 
     The nucleic acid probe for detecting human Th17 cells may include a set of two or more primers for amplifying the polynucleotide marker by nucleic acid amplification methods such as PCR technique, for example. 
     A molecule that can specifically bind to the present protein marker can be used for the detection of the marker, making it useful in the detection of human Th17 cells. Such molecule may be a nucleic acid aptamer such as DNA or RNA, an antibody, a ligand or a receptor that can specifically bind to the present protein marker, and preferably an antibody. 
     When the protein marker for detecting human Th17 cells is an enzyme, it can be detected by applying a substrate for the enzyme to develop color or emit light or fluorescent. 
     The antibody for detecting human Th17 cells can be prepared by the following well-known procedure, for example. A DNA molecule encoding a protein having an amino acid sequence of the present protein marker is prepared based on the nucleic acid sequence of the present polynucleotide marker or the amino acid sequence of the present protein marker, and is introduced into an appropriate expression vector. The obtained expression vector is introduced into an appropriate host cells, and the obtained transformed cells are cultured to obtain a desired protein. The obtained protein is purified and used as an immunogen optionally with an adjuvant to immunize an appropriate mammal such as rat or mouse. Spleen cells of the immunized animals are screened for antibody producing cells that produce an antibody directed to the target immunogen. The selected antibody producing cells are fused with myeloma cells to obtain hybridomas. These hybridomas are screened for antibody producing hybridomas that produce an antibody having specific binding property to the protein encoded by the gene. The desired antibody can be obtained by culturing the obtained antibody producing hybridomas. 
     The nucleic acid aptamer that can be used for detecting human Th17 cells can be prepared by the following well-known procedure, for example. A nucleic acid library including random nucleic acid sequences is prepared according to the known technique, and an aptamer that specifically binds to the target protein (the protein marker) can be selected by the systematic evolution of ligands by exponential enrichment method (SELEX method) or the like. 
     The molecule which can specifically bind to the protein marker for detecting human Th17 cells may be labeled with a labeling substance normally used in the art. The labeled antibody for detecting human Th17 cells allows an easy detection of the protein marker for detecting human Th17 cells, namely of human Th17 cells. 
     The labeling substance may be a labeling substance generally used in the art including radioisotopes such as  32 P, fluorescent substances such as fluorescein, enzymes such as alkaline phosphatase and horseradish peroxidase, and biotin. 
     A method for detecting human Th17 cells by detecting the presence of at least one polynucleotide or protein marker for detecting human Th17 cells in a sample containing cells derived from human is also within the scope of the present invention. 
     In the method, it is preferred that two or more polynucleotide markers or protein markers for detecting human Th17 cells are detected in order to improve the detection sensitivity. 
     In the present method, the sample containing cells derived from human includes a biological sample obtained from human or a sample containing cultured human cells. The biological sample includes blood, tissue, synovial fluid, cerebrospinal fluid, pleural fluid, ascitic fluid and the like. 
     An embodiment of the method for detecting the presence of the polynucleotide marker for detecting human Th17 cells is described. 
     Nucleic acid (DNA or RNA) is extracted from a sample containing cells derived from human by a well-known method in the art such as the one using a phenolic extraction and ethanol precipitation or a commercial DNA extraction kit. 
     Then, the presence of the polynucleotide marker in the obtained nucleic acid sample is detected, preferably using the nucleic acid probe for detecting human Th17 cells. When the presence of the polynucleotide marker is detected by nucleic acid amplification method such as PCR, RT-PCR, real-time PCR, LAMP (Loop-mediated isothermal amplification) and the like, the nucleic acid probe for detecting human Th17 cells is preferably a primer set for amplifying the polynucleotide marker by a nucleic acid amplification method. 
     The presence of the polynucleotide marker for detecting human Th17 cells may also be detected by well-known methods in the art, for example hybridization methods such as Southern hybridization, Northern hybridization, fluorescence in situ hybridization (FISH), or DNA chip or microarray. Such methods are carried out under the stringent condition, and the hybridization of the nucleic acid probe for detecting human Th17 cells is detected by detecting the labeling substance and the like to detect the presence of the polynucleotide marker. 
     An embodiment of the method for detecting the presence of the protein marker for detecting human Th17 cells is described. 
     When the target protein marker is an intracellular protein, proteins are extracted from a sample containing cells derived from human by using well-known methods in the art. The extraction of proteins from a sample can be accomplished by known methods such as disruption of the cells by ultrasonic, lysis of the cells with a cell lysis solution. The protein marker in the obtained protein extract can be detected by using the molecule which specifically binds to the protein marker. Specifically, the protein marker for detecting human Th17 cells can be detected by well-known methods in the art such as ELISA or Western blotting. The molecule which specifically binds to the protein marker in the detection is preferably the above nucleic acid aptamer, antibody, ligand or receptor, and more preferably the antibody for detecting human Th17 cells. 
     When the target protein marker is a secretory protein, the protein marker secreted in the sample containing the cells can be detected by using the molecule which specifically binds to the protein marker. 
     Alternatively, the cells (lymphocytes) are recovered from the sample containing the cells from human and the obtained cells are stimulated with anti-CD3 antibody, anti-CD28 antibody, concanavalin A, phytohemagglutinin (PHA), phorbol myristate acetate (PMA), ionomycin or the like. Then, the secreted protein marker can be detected by using the molecule which specifically binds to the protein marker. 
     Specifically, the protein marker can be detected by well-known methods in the art such as ELISA or Western blotting. The molecule which specifically binds to the protein marker in the detection is preferably the above nucleic acid aptamer, antibody, ligand or receptor, and more preferably the antibody for detecting human Th17 cells. 
     When the target protein marker is a protein located on the cell surface, the protein marker located on the cell surface in the sample containing the cells derived from human can be detected by using the molecule which specifically binds to the protein marker. 
     Alternatively, a membrane fraction of the cells is obtained from the sample containing the cells derived from human and the protein marker in the membrane fraction can be detected by using the molecule which specifically binds to the protein marker. Specifically, the protein marker can be detected by well-known methods in the art such as ELISA, Western blotting or a method based on flow cytometry (FCM). The molecule which specifically binds to the protein marker in the detection is preferably the above nucleic acid aptamer, antibody, ligand or receptor, and more preferably the antibody for detecting human Th17 cells. 
     For example, the protein marker for detecting human Th17 cells can be detected by FCM as follows. 
     First, the sample containing the cells derived from human is brought into contact with the antibody for detecting human Th17 cells labeled with an appropriate labeling substance. Human Th17 cells, when exist, bind to the labeled antibody on their surfaces. Then, the sample containing the cells bound to the labeling substance can be applied to a flow cytometer to detect human Th17 cells. Human Th17 cells that have bound to the labeling substance can optionally be classified and fractionated by using a cell sorter. 
     Such method of FCM is well-known to a person skilled in the art and he can appropriately select the reaction conditions. 
     The present invention also provides a reagent for detecting human Th17 cells which can be used in the present method for detecting human Th17 cells 
     The reagent comprises at least one substance selected from a nucleic acid probe which specifically hybridizes to the polynucleotide marker for detecting human Th17 cells, and a nucleic acid aptamer, antibody, ligand and receptor which specifically binds to the protein marker for detecting human Th17 cells. 
     The present invention is now described in detail by way of Examples, which do not limit the present invention. 
     EXAMPLE 1 
     Analysis of Highly Expressed Genes in Cultured Th17 Cells Derived from Human Peripheral Blood 
     1. Isolation of Th1, Th2, Treg and Th17 Cells from Human Peripheral Blood 
     (1) Isolation of Th1, Th2 and Th17 Cells from Human Peripheral Blood 
     Buffy coat obtained from peripheral blood of a healthy adult was overlaid on Ficoll-paque plus solution (GE Healthcare Bioscience) and centrifuged to obtain a monocyte fraction. Crude CD4 positive cells were purified from the fraction by using magnetic beads bound to anti-CD4 antibody (Miltenyi Biotec). 
     The obtained CD4 positive cells were stained with the fluorescence labeled antibodies shown in Table 1 and then Th1, Th2 and Th17 cells were separated by a cell sorter (FACS Aria: Becton Dickinson). The separation was carried out with the gating shown in Table 2. 
     
       
         
           
               
               
               
               
             
               
                 TABLE 1 
               
               
                   
               
               
                   
                 Fluorescence 
                   
                   
               
               
                 Antigen 
                 labeling substance 
                 Clone 
                 Manufacturer 
               
               
                   
               
             
            
               
                 CD4 
                 APC-Cy7 
                 RPA-T4 
                 BD Biosciences 
               
               
                 CD25 
                 PE-Cy7 
                 BC96 
                 eBioscience 
               
               
                 CXCR3 
                 Alexa Fluor ™ 488 
                 1C6/CXCR3 
                 BD Biosciences 
               
               
                 CCR4 
                 APC 
                 FAB1567A 
                 R&amp;D systems 
               
               
                 CCR6 
                 PE 
                 11A9 
                 BD Biosciences 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
             
               
                   
                 TABLE 2 
               
               
                   
                   
               
               
                   
                 Cell 
                 Gating 
               
               
                   
                   
               
             
            
               
                   
                 Th1 
                 CD4 high  CD25 low-negative  CXCR3 +  CCR6 −  CCR4 −   
               
               
                   
                 Th2 
                 CD4 high  CD25 low-negative  CXCR3 −  CCR6 −  CCR4 +   
               
               
                   
                 Th17 
                 CD4 high  CD25 low-negative  CXCR3 −  CCR6 +  CCR4 +   
               
               
                   
                   
               
            
           
         
       
     
     The above gating is described in detail in the reference by Acosta-Rodriguez E V et al. (Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells, Nat Immunol., 2007, vol. 8, p. 639-646). 
     (2) Isolation of Treg Cells from Human Peripheral Blood 
     CD4 positive cells obtained in the same manner as the above (1) were stained with the fluorescence labeled antibodies shown in Table 3, and CD4high CD25high CD127internal-negative cells were purified as Treg cells by using the above cell sorter. 
     
       
         
           
               
               
               
               
             
               
                 TABLE 3 
               
               
                   
               
               
                   
                 Fluorescence 
                   
                   
               
               
                 Antigen 
                 Labeling substance 
                 Clone 
                 Manufacturer 
               
               
                   
               
             
            
               
                 CD4 
                 FITC 
                 OKT4 
                 eBioscience 
               
               
                 CD25 
                 PE-Cy7 
                 BC96 
                 eBioscience 
               
               
                 GD45RO 
                 PE 
                 UCHL1 
                 BioLegend 
               
               
                 CD127 
                 Alexa Fluor ™ 647 
                 HIL-7R-M21 
                 BD Biosciences 
               
               
                   
               
            
           
         
       
     
     The above gating is described in detail in the reference by Weihong Liu et al. (CD 127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells, J Exp Med. 2006, vol. 203, p. 1701-1711). 
     2. Cell Culture 
     (1) Th1, Th2 and Th17 Cell Cultures 
     Th1, Th2 and Th17 cells derived from adult peripheral blood obtained in the above step 1. (1) were respectively plated in a 96-well plate at the density of 1.5×10 5  cells/0.3 ml/well. The medium used was Yssel medium (IMDM, 1% human serum of AB-type, 0.25% BSA, 1.8 mg/l 2-aminomethanol, 40 mg/l transferrin, 5 mg/l insulin, 2 mg/l linoleic acid, 2 mg/l oleic acid, 2 mg/l palmitic acid, 1% penicillin/streptomycin). 
     For activation and proliferation of the above cells, magnetic beads coated with anti-CD2/3/28 antibody (Miltenyi Biotec) (hereinafter also referred to as “antibody beads”) were added at 0.75×10 5  per well. After addition of cytokines and neutralizing antibody(s) suitable for differentiation culture of respective Th1, Th2 and Th17 cells, cells were incubated in an incubator at 37° C. with 5% CO 2 . Cytokines and neutralizing antibodies used are shown in Table 4. 
     
       
         
           
               
               
               
             
               
                 TABLE 4 
               
               
                   
               
               
                 Cell 
                 Cytokine 
                 Neutralizing antibody (Clone) 
               
               
                   
               
             
            
               
                 Th1 
                 IL-12, IL-2 
                 Anti-IL-4 antibody (MP4-25D2) 
               
               
                 Th2 
                 IL-4, IL-2 
                 Anti-IFN-γ antibody (R4-6A2) 
               
               
                 Th17 
                 TGF-β1, IL-6, IL-23, 
                 Anti-IL-4 antlbody (MP4-25D2), 
               
               
                   
                 IL-21, IL-1β, TNFα, IL-2 
                 Anti-IFN-γ antibody (R4-6A2) 
               
               
                   
               
            
           
         
       
     
     The concentrations of the above cytokines were 50 ng/ml for IL-6 and 10 ng/ml for other than IL-6. 
     The concentrations of antibodies were 10 μg/ml for anti-IFN-γ antibody and 2.5 μg/ml for anti-IL-4 antibody. The cytokines and neutralizing antibodies were obtained from R&amp;D systems and eBioscience, respectively. 
     After three days from the start of culture, cells were diluted three-fold with the medium containing the above cytokines and antibody(s) and cultured for further seven days (10 days in total). 
     After ten days from the start of culture, the obtained Th1, Th2 and Th17 cells were respectively divided into two equal parts, and one was washed with Yssel medium and PBS before centrifugation to collect cells, which were stored at −80° C. until the subsequent RNA extraction step. These cells were designated as Th1, Th2 and Th17 cells “without activation stimulation”. The other half was added with the antibody beads and cultured for three more hours to re-activate the cells. The cells were collected by centrifugation and similarly stored at −80° C. These cells were designated as Th1, Th2 and Th17 cells “with activation stimulation”. 
     (2) Treg Cell Culture 
     Treg cells obtained in the above step 1. (2) were cultured in the same manner in Yssel medium as the above step 2. (1) and activated with the antibody beads. To the medium were added cytokines IL-2 and TGF-β1 (R&amp;D systems), and neutralizing antibodies anti-IFN-γ antibody, anti-IL-4 antibody (eBioscience) and anti-IL-6 antibody (BD Bioscience). 
     These cytokines and neutralizing antibodies were used at the concentrations of 10 ng/ml and 5 μg/ml, respectively. 
     After three days from the start of culture, cells were added with the cytokines and neutralizing antibodies at the same amounts as those at the start of the culture. After culturing for three more days, cells were divided into two equal parts, one half was not added with the antibody beads used for activation and the other half was added with the antibody beads before culturing further three hours, thereby obtaining Treg cells “without activation stimulation” and Treg cells “with activation stimulation”, respectively. The cells were then collected by centrifugation and stored at −80° C. until the subsequent RNA extraction step. 
     3. Extraction of Total RNA 
     The cells obtained as the above step 2. were subjected to extraction of total RNAs using RNeasy Plus Mini kit and RNeasy micro kit (QIAGEN). 
     The specific procedures were according to the attached instructions of the kits. 
     4. Expression Analysis by Microarray 
     Total RNAs (10 to 100 ng) extracted from the cells as the above step 3. were reverse-transcribed to cDNAs with Two-Cycle Target Labeling and Control Reagents (Affymetrix), and further transcribed to biotinylated-cRNAs. The amplified biotinylated-cRNAs (20 μg) were fragmented. The specific procedures were according to the attached instruction of the kit. 
     The biotinylated-cRNAs derived from the cells as obtained above (15 μg) were applied to GeneChip Human Genome U-133 Plus 2.0 Array (Affymetrix) as samples, transferred to GeneChip Hybridization Oven 640 (Affymetrix) and hybridized under the conditions of 45° C. and 60 rpm for 16 hours. 
     After completion of the hybridization, the microarray was washed and fluorescence-labeled in GeneChip Fluidic Station 450 (Affymetrix), and scanned in GeneChip Scanner 3000 7G (Affymetrix) to obtain fluorescent intensity data. 
     5. Selection of Genes Specifically Expressed in Human Th17 Cells 
     The fluorescent data obtained in the above step 4. was standardized with the expression analysis software GeneSpring Ver. 10 (Agilent Technologies) based on MAS5 algorithm. Relative fluorescent intensities of the genes from Th17 cells were compared with those from Th1, Th2 and Treg cells. 
     The genes whose relative fluorescent intensities in Th17 cells were three or more times higher than any of those of Th1, Th2 and Treg cells and which were significantly expressed (which showed “p value &lt;0.05” after ANOVA test between four groups of relative fluorescent intensities in Th1, Th2, Treg and Th17 cells) were identified as the genes which were specifically expressed in Th17 cells. 
     The number of samples used in the above selection step is shown in Table 5. 
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 5 
               
               
                   
               
               
                   
                 Th1 
                 Th2 
                 Th17 
                 Treg 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 w/ activation stimulation 
                 5 
                 5 
                 5 
                 4 
               
               
                 w/o activation stimulation 
                 5 
                 5 
                 5 
                 3 
               
               
                   
               
            
           
         
       
     
     The genes specifically expressed in Th17 cells “without activation stimulation” and “with activation stimulation” are shown in Tables 6 and 7, respectively. 
     
       
         
           
               
             
               
                 TABLE 6 
               
             
            
               
                   
               
               
                 Without activation stimulation 
               
            
           
           
               
               
            
               
                   
                 Expression ratio 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Location of 
                   
                 Entrez 
                 Protein 
                 Transcript 
                 UniGene 
                 Probe Set 
                 Th17/ 
                   
                   
               
               
                 encoded protein 
                 Gene symbol 
                 Gene ID 
                 ID 
                 ID 
                 ID 
                 ID 
                 Th1 
                 Th17/Th2 
                 Th17/Treg 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Membrane 
                 ADAM12 
                 8038 
                 NP_003465, 
                 NM_003474, 
                 Hs.594537 
                 202952_s_at 
                 21.8 
                 80.1 
                 3.2 
               
               
                   
                   
                   
                 NP_067673 
                 NM_021641 
               
               
                   
                 ANKS1B 
                 56899 
                 NP_064525, 
                 NM_020140, 
                 Hs.506458 
                 227439_at 
                 6.9 
                 11.7 
                 4.3 
               
               
                   
                   
                   
                 NP_690001, 
                 NM_152788, 
                   
                 240292_x_at 
                 7.8 
                 10.3 
                 4.6 
               
               
                   
                   
                   
                 NP_858056 
                 NM_181670 
               
               
                   
                 ATP6V0A4 
                 50617 
                 NP_065683, 
                 NM_020632, 
                 Hs.98967 
                 220197_at 
                 22.8 
                 244.1 
                 153.8 
               
               
                   
                   
                   
                 NP_570855, 
                 NM_130840, 
               
               
                   
                   
                   
                 NP_570856 
                 NM_130841 
               
               
                   
                 ATP9A 
                 10079 
                 NP_006036 
                 NM_006045 
                 Hs.714307 
                 212062_at 
                 5.7 
                 53.5 
                 44.3 
               
               
                   
                 BVES 
                 11149 
                 NP_009004, 
                 NM_007073, 
                 Hs.221660 
                 228783_at 
                 3.0 
                 6.5 
                 16.2 
               
               
                   
                   
                   
                 NP_671488 
                 NM_147147 
               
               
                   
                 C5orf40 
                 408263 
                 NP_001001343 
                 NM_001001343 
                 Hs.437066 
                 1554801_at 
                 9.4 
                 12.8 
                 3.1 
               
               
                   
                 CDH4 
                 1002 
                 NP_001785 
                 NM_001794 
                 Hs.473231 
                 206866_at 
                 19.2 
                 16.0 
                 7.6 
               
               
                   
                 DIO2 
                 1734 
                 NP_000784, 
                 NM_000793, 
                 Hs.202354 
                 203700_s_at 
                 9.2 
                 3.4 
                 17.1 
               
               
                   
                   
                   
                 NP_001007024, 
                 NM_001007023, 
               
               
                   
                   
                   
                 NP_054644 
                 NM_013989 
               
               
                   
                 DMD 
                 1756 
                 NP_000100, 
                 NM_000109, 
                 Hs.495912 
                 203881_s_at 
                 10.3 
                 3.2 
                 10.0 
               
               
                   
                   
                   
                 NP_003997, 
                 NM_004006, 
               
               
                   
                   
                   
                 NP_003998, 
                 NM_004007, 
               
               
                   
                   
                   
                 NP_004000, 
                 NM_004009, 
               
               
                   
                   
                   
                 NP_004001, 
                 NM_004010, 
               
               
                   
                   
                   
                 NP_004002, 
                 NM_004011, 
               
               
                   
                   
                   
                 NP_004003, 
                 NM_004012, 
               
               
                   
                   
                   
                 NP_004004, 
                 NM_004013, 
               
               
                   
                   
                   
                 NP_004005, 
                 NM_004014, 
               
               
                   
                   
                   
                 NP_004006, 
                 NM_004015, 
               
               
                   
                   
                   
                 NP_004007, 
                 NM_004016, 
               
               
                   
                   
                   
                 NP_004008, 
                 NM_004017, 
               
               
                   
                   
                   
                 NP_004009, 
                 NM_004018, 
               
               
                   
                   
                   
                 NP_004010, 
                 NM_004019, 
               
               
                   
                   
                   
                 NP_004011, 
                 NM_004020, 
               
               
                   
                   
                   
                 NP_004012, 
                 NM_004021, 
               
               
                   
                   
                   
                 NP_004013, 
                 NM_004022, 
               
               
                   
                   
                   
                 NP_004014 
                 NM_004023 
               
               
                   
                 DRD2 
                 1813 
                 NP_000786, 
                 NM_000795, 
                 Hs.73893 
                 216938_x_at 
                 5.3 
                 5.6 
                 5.4 
               
               
                   
                   
                   
                 NP_057658 
                 NM_016574 
               
               
                   
                 GJC1 
                 10052 
                 NP_001073852, 
                 NM_001080383, 
                 Hs.532593 
                 228776_at 
                 7.0 
                 10.7 
                 4.9 
               
               
                   
                   
                   
                 NP_005488 
                 NM_005497 
                   
                 243502_at 
                 3.8 
                 10.5 
                 8.3 
               
               
                   
                 GPR34 
                 2857 
                 NP_001091048, 
                 NM_001097579, 
                 Hs.495989 
                 223620_at 
                 4.2 
                 7.9 
                 7.0 
               
               
                   
                   
                   
                 NP_005291 
                 NM_005300 
               
               
                   
                 IL23R 
                 149233 
                 NP_653302 
                 NM_144701 
                 Hs.677426 
                 1552912_a_at 
                 8.2 
                 15.3 
                 4.1 
               
               
                   
                 IRS2 
                 8660 
                 NP_003740 
                 NM_003749 
                 Hs.442344 
                 209184_s_at 
                 3.5 
                 4.0 
                 3.3 
               
               
                   
                   
                   
                   
                   
                   
                 209185_s_at 
                 6.0 
                 5.9 
                 4.3 
               
               
                   
                 KCNE3 
                 10008 
                 NP_005463 
                 NM_005472 
                 Hs.523899 
                 227647_at 
                 9.8 
                 8.3 
                 5.9 
               
               
                   
                 L1CAM 
                 3897 
                 NP_000416, 
                 NM_000425, 
                 Hs.522818 
                 204584_at 
                 8.5 
                 9.4 
                 5.1 
               
               
                   
                   
                   
                 NP_076493 
                 NM_024003 
               
               
                   
                 PGBD5, 
                 79605, 
                 NP_078830, 
                 NM_024554, 
                 Hs.520463 
                 219225_at 
                 9.9 
                 17.3 
                 11.3 
               
               
                   
                 LOC100134440 
                 100134440 
                 XP_001716155 
                 XM_001716103 
               
               
                   
                 MCAM 
                 4162 
                 NP_006491 
                 NM_006500 
                 Hs.599039 
                 210869_s_at 
                 9.5 
                 18.0 
                 5.6 
               
               
                   
                 MFAP3L 
                 9848 
                 NP_001009554, 
                 NM_001009554, 
                 Hs.593942 
                 205442_at 
                 11.5 
                 29.9 
                 7.1 
               
               
                   
                   
                   
                 NP_067679 
                 NM_021647 
               
               
                   
                 MS4A7 
                 58475 
                 NP_067024, 
                 NM_021201, 
                 Hs.530735 
                 223343_at 
                 16.6 
                 11.7 
                 3.2 
               
               
                   
                   
                   
                 NP_996821, 
                 NM_206938, 
               
               
                   
                   
                   
                 NP_996822, 
                 NM_206939, 
               
               
                   
                   
                   
                 NP_996823 
                 NM_206940 
               
               
                   
                 MYO7A 
                 4647 
                 NP_000251, 
                 NM_000260, 
                 Hs.370421 
                 208189_s_at 
                 19.4 
                 22.9 
                 6.5 
               
               
                   
                   
                   
                 NP_001120651, 
                 NM_001127179, 
               
               
                   
                   
                   
                 NP_001120652 
                 NM_001127180 
               
               
                   
                 ODZ4 
                 26011 
                 NP_001092286 
                 NM_001098816 
                 Hs.213087 
                 213273_at 
                 9.8 
                 13.1 
                 7.0 
               
               
                   
                 PHKA1 
                 5255 
                 NP_001116142, 
                 NM_001122670, 
                 Hs.201379 
                 229876_at 
                 4.2 
                 3.7 
                 15.8 
               
               
                   
                   
                   
                 NP_002628 
                 NM_002637 
               
               
                   
                 PTPRM 
                 5797 
                 NP_001098714, 
                 NM_001105244, 
                 Hs.49774 
                 1555579_s_at 
                 3.6 
                 76.0 
                 3.7 
               
               
                   
                   
                   
                 NP_002836 
                 NM_002845 
               
               
                   
                 RGS1 
                 5996 
                 NP_002913 
                 NM_002922 
                 Hs.75256 
                 202988_s_at 
                 3.3 
                 3.6 
                 3.9 
               
               
                   
                 SHB 
                 6461 
                 NP_003019 
                 NM_003028 
                 Hs.521482 
                 1557458_s_at 
                 14.9 
                 27.8 
                 7.4 
               
               
                   
                 SHROOM2 
                 357 
                 NP_001640 
                 NM_001649 
                 Hs.567236 
                 204967_at 
                 3.4 
                 3.4 
                 3.4 
               
               
                   
                 SLC16A4 
                 9122 
                 NP_004687 
                 NM_004696 
                 Hs.351306 
                 205234_at 
                 66.3 
                 20.4 
                 3.4 
               
               
                   
                 SLC44A3 
                 126969 
                 NP_001107578, 
                 NM_001114106, 
                 Hs.483423 
                 228221_at 
                 3.1 
                 9.3 
                 3.5 
               
               
                   
                   
                   
                 NP_689582 
                 NM_152369 
               
               
                   
                 SLC6A15 
                 55117 
                 NP_060527, 
                 NM_018057, 
                 Hs.44424 
                 206376_at 
                 10.7 
                 11.9 
                 15.2 
               
               
                   
                   
                   
                 NP_877499 
                 NM_182767 
               
               
                   
                 SLCO2B1 
                 11309 
                 NP_009187 
                 NM_007256 
                 Hs.7884 
                 203473_at 
                 9.7 
                 6.0 
                 6.8 
               
               
                   
                 SYNGR3 
                 9143 
                 NP_004200 
                 NM_004209 
                 Hs.435277 
                 205691_at 
                 4.7 
                 7.9 
                 5.5 
               
               
                   
                 TANC2 
                 26115 
                 NP_079461 
                 NM_025185 
                 Hs.410889 
                 208425_s_at 
                 4.7 
                 9.0 
                 7.3 
               
               
                   
                   
                   
                   
                   
                   
                 224952_at 
                 6.1 
                 5.8 
                 7.5 
               
               
                   
                 TJP1 
                 7082 
                 NP_003248, 
                 NM_003257, 
                 Hs.716406 
                 202011_at 
                 15.3 
                 19.2 
                 4.3 
               
               
                   
                   
                   
                 NP_783297 
                 NM_175610 
               
               
                   
                 TMEM163 
                 81615 
                 NP_112185 
                 NM_030923 
                 Hs.369471 
                 1552626_a_at 
                 16.1 
                 32.5 
                 16.4 
               
               
                   
                   
                   
                   
                   
                   
                 223503_at 
                 28.8 
                 47.9 
                 29.7 
               
               
                   
                 TNS3 
                 64759 
                 NP_073585 
                 NM_022748 
                 Hs.520814 
                 217853_at 
                 7.6 
                 158.8 
                 4.5 
               
               
                   
                 UPK1B 
                 7348 
                 NP_008883 
                 NM_006952 
                 Hs.271580 
                 210065_s_at 
                 5.8 
                 7.5 
                 4.6 
               
               
                   
                 WDFY3 
                 23001 
                 NP_055806, 
                 NM_014991, 
                 Hs.480116 
                 212598_at 
                 14.2 
                 18.4 
                 45.6 
               
               
                   
                   
                   
                 NP_848698, 
                 NM_178583, 
                   
                 212602_at 
                 18.7 
                 56.1 
                 29.3 
               
               
                   
                   
                   
                 NP_848700 
                 NM_178585 
                   
                 212606_at 
                 23.0 
                 82.7 
                 71.7 
               
               
                 Extracellular/ 
                 C17orf99 
                 100141515 
                 NP_001156547 
                 NM_001163075 
                 Hs.633034 
                 236981_at 
                 29.1 
                 10.9 
                 4.1 
               
               
                 secreted 
                 CXCL13 
                 10563 
                 NP_006410 
                 NM_006419 
                 Hs.100431 
                 205242_at 
                 57.7 
                 20.1 
                 4.6 
               
               
                   
                 EBI3 
                 10148 
                 NP_005746 
                 NM_005755 
                 Hs.501452 
                 219424_at 
                 3.6 
                 43.8 
                 3.7 
               
               
                   
                 IL17A 
                 3605 
                 NP_002181 
                 NM_002190 
                 Hs.41724 
                 216876_s_at 
                 340.3 
                 618.9 
                 21.8 
               
               
                   
                 IL17F 
                 112744 
                 NP_443104 
                 NM_052872 
                 Hs.272295 
                 234408_at 
                 559.0 
                 778.4 
                 525.7 
               
               
                   
                 IL1A 
                 3552 
                 NP_000566 
                 NM_000575 
                 Hs.1722 
                 210118_s_at 
                 38.1 
                 13.8 
                 6.5 
               
               
                   
                 IL22 
                 50616 
                 NP_065386 
                 NM_020525 
                 Hs.287369 
                 222974_at 
                 7.5 
                 26.0 
                 13.6 
               
               
                   
                 IL26 
                 55801 
                 NP_060872 
                 NM_018402 
                 Hs.272350 
                 221111_at 
                 11.6 
                 13.5 
                 53.7 
               
               
                   
                 IL9 
                 3578 
                 NP_000581 
                 NM_000590 
                 Hs.960 
                 208193_at 
                 103.8 
                 193.5 
                 24.1 
               
               
                   
                 PCOLCE2 
                 26577 
                 NP_037495 
                 NM_013363 
                 Hs.8944 
                 219295_s_at 
                 10.6 
                 16.8 
                 25.3 
               
               
                   
                 PNOC 
                 5368 
                 NP_006219 
                 NM_006228 
                 Hs.88218 
                 205901_at 
                 36.8 
                 27.3 
                 69.3 
               
               
                   
                 SMPDL3A 
                 10924 
                 NP_006705 
                 NM_006714 
                 Hs.486357 
                 213624_at 
                 4.0 
                 3.8 
                 7.9 
               
               
                   
                 TGFBI 
                 7045 
                 NP_000349 
                 NM_000358 
                 Hs.369397 
                 201506_at 
                 54.7 
                 476.7 
                 33.8 
               
               
                   
                 WNT3 
                 7473 
                 NP_110380 
                 NM_030753 
                 Hs.445884 
                 229103_at 
                 6.6 
                 5.9 
                 6.2 
               
               
                 Intracellular 
                 BCAT1 
                 586 
                 NP_005495 
                 NM_005504 
                 Hs.438993 
                 214390_s_at 
                 3.1 
                 4.1 
                 18.9 
               
               
                   
                   
                   
                   
                   
                   
                 214452_at 
                 3.5 
                 6.4 
                 24.8 
               
               
                   
                   
                   
                   
                   
                   
                 225285_at 
                 3.0 
                 3.5 
                 31.5 
               
               
                   
                   
                   
                   
                   
                   
                 226517_at 
                 3.1 
                 3.5 
                 38.3 
               
               
                   
                 BHLHE22 
                 27319 
                 NP_689627 
                 NM_152414 
                 Hs.591870 
                 228636_at 
                 18.9 
                 24.7 
                 40.5 
               
               
                   
                 C13orf18, 
                 80183, 
                 NP_079389, 
                 NM_025113, 
                 Hs.98117 
                 44790_s_at 
                 3.2 
                 11.2 
                 32.0 
               
               
                   
                 LOC728970 
                 728970 
                 XP_001132115, 
                 XM_001132115, 
               
               
                   
                   
                   
                 XP_001133896, 
                 XM_001133896, 
               
               
                   
                   
                   
                 XP_001720207 
                 XM_001720155 
               
               
                   
                 CA2 
                 760 
                 NP_000058 
                 NM_000067 
                 Hs.155097 
                 209301_at 
                 6.3 
                 452.7 
                 103.6 
               
               
                   
                 CCDC3 
                 83643 
                 NP_113643 
                 NM_031455 
                 Hs.498720 
                 223316_at 
                 16.3 
                 106.1 
                 42.1 
               
               
                   
                 CDS1 
                 1040 
                 NP_001254 
                 NM_001263 
                 Hs.654899 
                 205709_s_at 
                 13.9 
                 26.7 
                 3.8 
               
               
                   
                 CHN1 
                 1123 
                 NP_001020372, 
                 NM_001025201, 
                 Hs.654534 
                 212624_s_at 
                 6.9 
                 12.3 
                 6.4 
               
               
                   
                   
                   
                 NP_001813 
                 NM_001822 
               
               
                   
                 CLIC5, 
                 53405, 
                 NP_001107558, 
                 NM_001114086, 
                 Hs.485489 
                 213317_at 
                 6.7 
                 53.5 
                 13.3 
               
               
                   
                 LOC100131610 
                 100131610 
                 NP_058625, 
                 NM_016929, 
                   
                 217628_at 
                 3.1 
                 9.1 
                 4.2 
               
               
                   
                   
                   
                 XP_001723610 
                 XM_001723558 
                   
                 243917_at 
                 13.9 
                 56.8 
                 16.7 
               
               
                   
                   
                   
                   
                   
                   
                 219866_at 
                 7.1 
                 28.2 
                 17.8 
               
               
                   
                 CTSH 
                 1512 
                 NP_004381, 
                 NM_004390, 
                 Hs.148641 
                 202295_s_at 
                 4.7 
                 10.4 
                 5.6 
               
               
                   
                   
                   
                 NP_683880 
                 NM_148979 
               
               
                   
                 CYP7B1 
                 9420 
                 NP_004811 
                 NM_004820 
                 Hs.667720 
                 207386_at 
                 12.3 
                 10.2 
                 4.1 
               
               
                   
                 DAPK2 
                 23604 
                 NP_055141 
                 NM_014326 
                 Hs.237886 
                 206324_s_at 
                 7.3 
                 9.9 
                 8.3 
               
               
                   
                   
                   
                   
                   
                   
                 215184_at 
                 6.3 
                 11.0 
                 7.1 
               
               
                   
                 DDIT4L 
                 115265 
                 NP_660287 
                 NM_145244 
                 Hs.480378 
                 228057_at 
                 3.1 
                 5.2 
                 106.8 
               
               
                   
                 DHRS9 
                 10170 
                 NP_001135742, 
                 NM_001142270, 
                 Hs.179608 
                 219799_s_at 
                 8.3 
                 14.6 
                 11.9 
               
               
                   
                   
                   
                 NP_001135743, 
                 NM_001142271, 
                   
                 223952_x_at 
                 5.3 
                 7.8 
                 7.7 
               
               
                   
                   
                   
                 NP_005762, 
                 NM_005771, 
                   
                 224009_x_at 
                 6.3 
                 7.9 
                 7.0 
               
               
                   
                   
                   
                 NP_954674 
                 NM_199204 
               
               
                   
                 DMRT1 
                 1761 
                 NP_068770 
                 NM_021951 
                 Hs.98586 
                 220493_at 
                 3.6 
                 16.6 
                 6.4 
               
               
                   
                 DSE 
                 29940 
                 NP_001074445, 
                 NM_001080976, 
                 Hs.486292 
                 218854_at 
                 13.9 
                 41.8 
                 26.2 
               
               
                   
                   
                   
                 NP_037484 
                 NM_013352 
               
               
                   
                 ERC2 
                 26059 
                 NP_056391 
                 NM_015576 
                 Hs.476389 
                 213938_at 
                 3.5 
                 6.1 
                 6.1 
               
               
                   
                 FBXL17 
                 64839 
                 NP_073735 
                 NM_022824 
                 Hs.657225 
                 227203_at 
                 8.9 
                 7.7 
                 4.7 
               
               
                   
                 FBXL21 
                 26223 
                 NP_036291 
                 NM_012159 
                 Hs.591275 
                 1555412_at 
                 22.9 
                 29.2 
                 13.0 
               
               
                   
                 FERMT2 
                 10979 
                 NP_001128471, 
                 NM_001134999, 
                 Hs.509343 
                 209210_s_at 
                 3.1 
                 9.5 
                 5.8 
               
               
                   
                   
                   
                 NP_001128472, 
                 NM_001135000, 
               
               
                   
                   
                   
                 NP_006823 
                 NM_006832 
               
               
                   
                 FHOD3 
                 80206 
                 NP_079411 
                 NM_025135 
                 Hs.436636 
                 218980_at 
                 7.2 
                 10.3 
                 7.8 
               
               
                   
                 H2AFY2 
                 55506 
                 NP_061119 
                 NM_018649 
                 Hs.499953 
                 218445_at 
                 5.2 
                 6.5 
                 6.4 
               
               
                   
                 HHEX 
                 3087 
                 NP_002720 
                 NM_002729 
                 Hs.118651 
                 204689_at 
                 3.6 
                 5.9 
                 6.4 
               
               
                   
                 HLX 
                 3142 
                 NP_068777 
                 NM_021958 
                 Hs.74870 
                 214438_at 
                 4.1 
                 8.4 
                 26.3 
               
               
                   
                 HS3ST1 
                 9957 
                 NP_005105 
                 NM_005114 
                 Hs.507348 
                 205466_s_at 
                 21.2 
                 6.0 
                 3.2 
               
               
                   
                 IRAK3 
                 11213 
                 NP_001135995, 
                 NM_001142523, 
                 Hs.369265 
                 213817_at 
                 14.5 
                 16.5 
                 6.0 
               
               
                   
                   
                   
                 NP_009130 
                 NM_007199 
                   
                 220034_at 
                 5.5 
                 10.3 
                 3.4 
               
               
                   
                 MACC1 
                 346389 
                 NP_877439 
                 NM_182762 
                 Hs.598388 
                 1566766_a_at 
                 5.9 
                 15.7 
                 3.5 
               
               
                   
                 MAML3 
                 55534 
                 NP_061187 
                 NM_018717 
                 Hs.586165 
                 242794_at 
                 5.4 
                 5.7 
                 4.1 
               
               
                   
                 MYO10 
                 4651 
                 NP_036466 
                 NM_012334 
                 Hs.481720 
                 201976_s_at 
                 39.5 
                 17.2 
                 7.1 
               
               
                   
                 NR5A2 
                 2494 
                 NP_003813, 
                 NM_003822, 
                 Hs.33446 
                 208343_s_at 
                 5.5 
                 17.9 
                 39.5 
               
               
                   
                   
                   
                 NP_995582 
                 NM_205860 
               
               
                   
                 OTUB2 
                 78990 
                 NP_075601 
                 NM_023112 
                 Hs.278815 
                 219369_s_at 
                 3.4 
                 3.7 
                 6.3 
               
               
                   
                   
                   
                   
                   
                   
                 222878_s_at 
                 3.2 
                 3.2 
                 6.6 
               
               
                   
                 PAPSS2 
                 9060 
                 NP_001015880, 
                 NM_001015880, 
                 Hs.524491 
                 203058_s_at 
                 4.4 
                 5.1 
                 19.5 
               
               
                   
                   
                   
                 NP_004661 
                 NM_004670 
                   
                 203060_s_at 
                 6.6 
                 17.0 
                 14.3 
               
               
                   
                 PCBP3 
                 54039 
                 NP_001123613, 
                 NM_001130141, 
                 Hs.474049 
                 230486_at 
                 4.1 
                 3.6 
                 4.8 
               
               
                   
                   
                   
                 NP_065389 
                 NM_020528 
               
               
                   
                 PDE4DIP 
                 9659 
                 NP_001002810, 
                 NM_001002810, 
                 Hs.654651 
                 205872_x_at 
                 4.3 
                 33.4 
                 3.3 
               
               
                   
                   
                   
                 NP_001002811, 
                 NM_001002811, 
                 Hs.613082 
                 209700_x_at 
                 4.1 
                 10.9 
                 9.5 
               
               
                   
                   
                   
                 NP_001002812, 
                 NM_001002812, 
               
               
                   
                   
                   
                 NP_055459, 
                 NM_014644, 
               
               
                   
                   
                   
                 NP_071754 
                 NM_022359 
               
               
                   
                 PHLDA1 
                 22822 
                 NP_031376 
                 NM_007350 
                 Hs.602085 
                 217999_s_at 
                 3.6 
                 5.0 
                 10.3 
               
               
                   
                   
                   
                   
                   
                   
                 225842_at 
                 3.3 
                 3.2 
                 8.0 
               
               
                   
                 PLD1 
                 5337 
                 NP_001123553, 
                 NM_001130081, 
                 Hs.382865 
                 177_at 
                 3.5 
                 3.4 
                 10.3 
               
               
                   
                   
                   
                 NP_002653 
                 NM_002662 
                   
                 215723_s_at 
                 3.9 
                 3.4 
                 11.4 
               
               
                   
                   
                   
                   
                   
                   
                 226636_at 
                 5.7 
                 3.6 
                 13.1 
               
               
                   
                 PPARG 
                 5468 
                 NP_005028, 
                 NM_005037, 
                 Hs.162646 
                 208510_s_at 
                 7.9 
                 134.5 
                 16.5 
               
               
                   
                   
                   
                 NP_056953, 
                 NM_015869, 
               
               
                   
                   
                   
                 NP_619725, 
                 NM_138711, 
               
               
                   
                   
                   
                 NP_619726 
                 NM_138712 
               
               
                   
                 PTPN13 
                 5783 
                 NP_006255, 
                 NM_006264, 
                 Hs.436142 
                 243792_x_at 
                 3.5 
                 4.2 
                 7.9 
               
               
                   
                   
                   
                 NP_542414, 
                 NM_080683, 
               
               
                   
                   
                   
                 NP_542415, 
                 NM_080684, 
               
               
                   
                   
                   
                 NP_542416 
                 NM_080685 
               
               
                   
                 RBM20 
                 282996 
                 NP_001127835, 
                 NM_001134363, 
                 Hs.715766 
                 238763_at 
                 8.0 
                 3.5 
                 3.0 
               
               
                   
                   
                   
                 XP_001716171, 
                 XM_001716119, 
               
               
                   
                   
                   
                 XP_291671, 
                 XM_291671, 
               
               
                   
                   
                   
                 XP_944430 
                 XM_939337 
               
               
                   
                 RGS18 
                 64407 
                 NP_570138 
                 NM_130782 
                 Hs.440890 
                 223809_at 
                 3.3 
                 6.9 
                 8.8 
               
               
                   
                 RORC 
                 6097 
                 NP_001001523, 
                 NM_001001523, 
                 Hs.256022 
                 228806_at 
                 14.0 
                 170.6 
                 7.7 
               
               
                   
                   
                   
                 NP_005051 
                 NM_005060 
               
               
                   
                 NINL 
                 22981 
                 NP_079452 
                 NM_025176 
                 Hs.696157 
                 207705_s_at 
                 4.7 
                 4.7 
                 3.1 
               
               
                   
                 RTN2 
                 6253 
                 NP_005610, 
                 NM_005619, 
                 Hs.47517 
                 34408_at 
                 3.7 
                 4.6 
                 4.5 
               
               
                   
                   
                   
                 NP_996783, 
                 NM_206900, 
               
               
                   
                   
                   
                 NP_996784 
                 NM_206901 
               
               
                   
                 SH3RF2 
                 153769 
                 NP_689763 
                 NM_152550 
                 Hs.443728 
                 243582_at 
                 5.8 
                 4.1 
                 18.5 
               
               
                   
                 SIM1 
                 6492 
                 NP_005059 
                 NM_005068 
                 Hs.520293 
                 1556300_s_at 
                 8.8 
                 4.8 
                 69.0 
               
               
                   
                   
                   
                   
                   
                   
                 206876_at 
                 8.7 
                 4.8 
                 37.5 
               
               
                   
                 SNAI2 
                 6591 
                 NP_003059 
                 NM_003068 
                 Hs.360174 
                 213139_at 
                 24.6 
                 22.5 
                 13.8 
               
               
                   
                 SOX2 
                 6657 
                 NP_003097 
                 NM_003106 
                 Hs.518438 
                 228038_at 
                 9.6 
                 8.3 
                 3.4 
               
               
                   
                 SPIRE1 
                 56907 
                 NP_001122098, 
                 NM_001128626, 
                 Hs.515283 
                 1554807_a_at 
                 4.7 
                 6.1 
                 3.8 
               
               
                   
                   
                   
                 NP_001122099, 
                 NM_001128627, 
                   
                 224995_at 
                 8.0 
                 9.0 
                 4.7 
               
               
                   
                   
                   
                 NP_064533 
                 NM_020148 
                   
                 225018_at 
                 6.6 
                 9.2 
                 6.3 
               
               
                   
                 TBC1D12 
                 23232 
                 NP_056003 
                 NM_015188 
                 Hs.500598 
                 221858_at 
                 7.7 
                 5.8 
                 5.5 
               
               
                   
                 TGM5 
                 9333 
                 NP_004236, 
                 NM_004245, 
                 Hs.129719 
                 207911_s_at 
                 3.6 
                 6.6 
                 5.1 
               
               
                   
                   
                   
                 NP_963925 
                 NM_201631 
               
               
                   
                 TMOD1 
                 7111 
                 NP_003266 
                 NM_003275 
                 Hs.494595 
                 203661_s_at 
                 7.0 
                 14.7 
                 5.1 
               
               
                   
                   
                   
                   
                   
                   
                 203662_s_at 
                 7.8 
                 14.5 
                 4.5 
               
               
                   
                 TSHZ2 
                 128553 
                 NP_775756 
                 NM_173485 
                 Hs.649877 
                 220213_at 
                 3.6 
                 12.4 
                 3.8 
               
               
                   
                   
                   
                   
                   
                 Hs.271605 
                 243940_at 
                 3.1 
                 10.6 
                 4.1 
               
               
                   
                 TUBB6 
                 84617 
                 NP_115914 
                 NM_032525 
                 Hs.193491 
                 209191_at 
                 4.1 
                 12.7 
                 4.7 
               
               
                 Unknown 
                 C1orf106 
                 55765 
                 NP_001136041, 
                 NM_001142569, 
                 Hs.518997 
                 219010_at 
                 78.5 
                 111.8 
                 3.3 
               
               
                   
                   
                   
                 NP_060735 
                 NM_018265 
               
               
                   
                 C6orf145 
                 221749 
                 NP_899229 
                 NM_183373 
                 Hs.484500 
                 212923_s_at 
                 10.4 
                 3.8 
                 5.2 
               
               
                   
                 LOC401097 
                 401097 
                 XP_001717155, 
                 XM_001717103, 
                 Hs.710781 
                 236738_at 
                 6.8 
                 3.3 
                 24.9 
               
               
                   
                   
                   
                 XP_001718614, 
                 XM_001718562, 
               
               
                   
                   
                   
                 XP_001718795 
                 XM_001718743 
               
               
                   
                 MAMLD1 
                 10046 
                 NP_005482 
                 NM_005491 
                 Hs.20136 
                 205088_at 
                 6.6 
                 8.3 
                 34.1 
               
               
                   
                 ZC3H12C 
                 85463 
                 NP_203748 
                 NM_033390 
                 Hs.376289 
                 231899_at 
                 3.0 
                 4.1 
                 18.7 
               
               
                   
                 — 
                 — 
                 — 
                 AA579799, 
                 Hs.663788 
                 215768_at 
                 4.1 
                 6.1 
                 6.7 
               
               
                   
                   
                   
                   
                 AA947186, 
               
               
                   
                   
                   
                   
                 AL049337, 
               
               
                   
                   
                   
                   
                 AW665328 
               
               
                   
                 — 
                 — 
                 — 
                 AK093229 
                 Hs.586723 
                 222900_at 
                 5.9 
                 3.0 
                 4.5 
               
               
                   
                 — 
                 — 
                 — 
                 AK055628, 
                 Hs.594351 
                 226777_at 
                 21.6 
                 39.7 
                 3.6 
               
               
                   
                   
                   
                   
                 uc001ljj.1 
               
               
                   
                 — 
                 — 
                 — 
                 AK129763, 
                 Hs.157726 
                 227452_at 
                 4.6 
                 4.2 
                 4.5 
               
               
                   
                   
                   
                   
                 CR595588, 
               
               
                   
                   
                   
                   
                 uc002jiy.1, 
               
               
                   
                   
                   
                   
                 uc002jiz.1 
               
               
                   
                 — 
                 — 
                 — 
                 AA416573, 
                 Hs.654918 
                 229951_x_at 
                 4.7 
                 15.0 
                 7.1 
               
               
                   
                   
                   
                   
                 AA628762, 
               
               
                   
                   
                   
                   
                 D53835, 
               
               
                   
                   
                   
                   
                 D53836, 
               
               
                   
                   
                   
                   
                 H24473, 
               
               
                   
                   
                   
                   
                 R37871, 
               
               
                   
                   
                   
                   
                 R40232, 
               
               
                   
                   
                   
                   
                 T10348, 
               
               
                   
                   
                   
                   
                 T23451, 
               
               
                   
                   
                   
                   
                 W56351, 
               
               
                   
                   
                   
                   
                 W57867, 
               
               
                   
                   
                   
                   
                 Z28733 
               
               
                   
                 — 
                 — 
                 — 
                 AI766299 
                 — 
                 236338_at 
                 4.3 
                 4.4 
                 3.3 
               
               
                   
                 — 
                 — 
                 — 
                 AI262017, 
                 Hs.666775 
                 237923_at 
                 6.9 
                 5.3 
                 4.0 
               
               
                   
                   
                   
                   
                 AI280978, 
               
               
                   
                   
                   
                   
                 AI284950, 
               
               
                   
                   
                   
                   
                 AI733224, 
               
               
                   
                   
                   
                   
                 AI733801 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
             
               
                 TABLE 7 
               
             
            
               
                   
               
               
                 Location of 
                 Expression ratio 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 encoded 
                   
                 Entrez 
                 Protein 
                 Transcript 
                 UniGene 
                 Probe Set 
                 Th17/ 
                 Th17/ 
                   
               
               
                 protein 
                 Gene symbol 
                 Gene ID 
                 ID 
                 ID 
                 ID 
                 ID 
                 Th1 
                 Th2 
                 Th17/Treg 
               
               
                   
               
            
           
           
               
            
               
                 Without activation stimulation 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Unknown 
                 — 
                 — 
                 — 
                 AA687415, 
                 Hs.434948 
                 238009_at 
                 4.0 
                 19.0 
                 27.6 
               
               
                   
                   
                   
                   
                 AA96901, 
               
               
                   
                   
                   
                   
                 AI291640, 
               
               
                   
                   
                   
                   
                 AI446064, 
               
               
                   
                   
                   
                   
                 AI634557, 
               
               
                   
                   
                   
                   
                 AI694948, 
               
               
                   
                   
                   
                   
                 AI701854, 
               
               
                   
                   
                   
                   
                 AI983938, 
               
               
                   
                   
                   
                   
                 AV745212, 
               
               
                   
                   
                   
                   
                 AV745909, 
               
               
                   
                   
                   
                   
                 AV746001, 
               
               
                   
                   
                   
                   
                 AW008696, 
               
               
                   
                   
                   
                   
                 AW511701, 
               
               
                   
                   
                   
                   
                 AW974416, 
               
               
                   
                   
                   
                   
                 BG149302, 
               
               
                   
                   
                   
                   
                 BG150103, 
               
               
                   
                   
                   
                   
                 N66771, 
               
               
                   
                   
                   
                   
                 R66991 
               
               
                   
                 — 
                 — 
                 — 
                 AI148241, 
                 Hs.659083 
                 238151_at 
                 50.6 
                 21.1 
                 24.4 
               
               
                   
                   
                   
                   
                 AI735444, 
               
               
                   
                   
                   
                   
                 BE645654, 
               
               
                   
                   
                   
                   
                 BF510855, 
               
               
                   
                   
                   
                   
                 BF511636 
               
               
                   
                 — 
                 — 
                 — 
                 AK094629 
                 Hs.594896 
                 238623_at 
                 4.9 
                 4.8 
                 3.4 
               
               
                   
                 — 
                 — 
                 — 
                 AI682088, 
                 Hs.606172 
                 241726_at 
                 5.4 
                 5.7 
                 9.5 
               
               
                   
                   
                   
                   
                 AI951058, 
               
               
                   
                   
                   
                   
                 F06296, 
               
               
                   
                   
                   
                   
                 F13164, 
               
               
                   
                   
                   
                   
                 T77624, 
               
               
                   
                   
                   
                   
                 Z44722 
               
            
           
           
               
            
               
                 With activation stimulation 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Membrane 
                 ADAM12 
                 8038 
                 NP_003465, 
                 NM_003474, 
                 Hs.594537 
                 202952_s_at 
                 19.5 
                 71.0 
                 3.5 
               
               
                   
                   
                   
                 NP_067673 
                 NM_021641 
               
               
                   
                 AKAP12 
                 9590 
                 NP_005091, 
                 NM_005100, 
                 Hs.371240 
                 210517_s_at 
                 9.8 
                 4.5 
                 12.8 
               
               
                   
                   
                   
                 NP_653080 
                 NM_144497 
                   
                 227529_s_at 
                 8.9 
                 5.7 
                 45.5 
               
               
                   
                 ANKS1B 
                 56899 
                 NP_064525, 
                 NM_020140, 
                 Hs.506458 
                 227439_at 
                 5.7 
                 10.5 
                 15.1 
               
               
                   
                   
                   
                 NP_690001, 
                 NM_152788, 
                   
                 227440_at 
                 3.6 
                 12.0 
                 6.3 
               
               
                   
                   
                   
                 NP_858056 
                 NM_181670 
                   
                 240292_x_at 
                 5.1 
                 9.9 
                 8.5 
               
               
                   
                 ATP6V0A4 
                 50617 
                 NP_065683, 
                 NM_020632, 
                 Hs.98967 
                 220197_at 
                 9.0 
                 96.4 
                 64.8 
               
               
                   
                   
                   
                 NP_570855, 
                 NM_130840, 
               
               
                   
                   
                   
                 NP_570856 
                 NM_130841 
               
               
                   
                 ATP9A 
                 10079 
                 NP_006036 
                 NM_006045 
                 Hs.714307 
                 212062_at 
                 7.5 
                 55.4 
                 46.4 
               
               
                   
                 BVES 
                 11149 
                 NP_009004, 
                 NM_007073, 
                 Hs.221660 
                 228783_at 
                 3.4 
                 5.9 
                 9.8 
               
               
                   
                   
                   
                 NP_671488 
                 NM_147147 
               
               
                   
                 C5orf40 
                 408263 
                 NP_001001343 
                 NM_001001343 
                 Hs.437066 
                 1554801_at 
                 17.2 
                 21.0 
                 5.4 
               
               
                   
                 C9orf125 
                 84302 
                 NP_115718 
                 NM_032342 
                 Hs.655738 
                 224458_at 
                 7.5 
                 5.2 
                 8.2 
               
               
                   
                 CDH4 
                 1002 
                 NP_001785 
                 NM_001794 
                 Hs.473231 
                 206866_at 
                 7.4 
                 13.7 
                 11.6 
               
               
                   
                 DIO2 
                 1734 
                 NP_000784, 
                 NM_000793, 
                 Hs.202354 
                 203699_s_at 
                 5.7 
                 8.0 
                 15.4 
               
               
                   
                   
                   
                 NP_001007024, 
                 NM_001007023, 
                   
                 203700_s_at 
                 12.2 
                 13.6 
                 14.1 
               
               
                   
                   
                   
                 NP_054644 
                 NM_013989 
                   
                 231240_at 
                 9.6 
                 5.3 
                 6.3 
               
               
                   
                 DMD 
                 1756 
                 NP_000100, 
                 NM_000109, 
                 Hs.495912 
                 203881_s_at 
                 9.7 
                 3.1 
                 10.4 
               
               
                   
                   
                   
                 NP_003997, 
                 NM_004006, 
               
               
                   
                   
                   
                 NP_003998, 
                 NM_004007, 
               
               
                   
                   
                   
                 NP_004000, 
                 NM_004009, 
               
               
                   
                   
                   
                 NP_004001, 
                 NM_004010, 
               
               
                   
                   
                   
                 NP_004002, 
                 NM_004011, 
               
               
                   
                   
                   
                 NP_004003, 
                 NM_004012, 
               
               
                   
                   
                   
                 NP_004004, 
                 NM_004013, 
               
               
                   
                   
                   
                 NP_004005, 
                 NM_004014, 
               
               
                   
                   
                   
                 NP_004006, 
                 NM_004015, 
               
               
                   
                   
                   
                 NP_004007, 
                 NM_004016, 
               
               
                   
                   
                   
                 NP_004008, 
                 NM_004017, 
               
               
                   
                   
                   
                 NP_004009, 
                 NM_004018, 
               
               
                   
                   
                   
                 NP_004010, 
                 NM_004019, 
               
               
                   
                   
                   
                 NP_004011, 
                 NM_004020, 
               
               
                   
                   
                   
                 NP_004012, 
                 NM_004021, 
               
               
                   
                   
                   
                 NP_004013, 
                 NM_004022, 
               
               
                   
                   
                   
                 NP_004014 
                 NM_004023 
               
               
                   
                 DPY19L2 
                 283417 
                 NP_776173 
                 NM_173812 
                 Hs.533644 
                 230158_at 
                 12.5 
                 13.0 
                 3.4 
               
               
                   
                 GPR34 
                 2857 
                 NP_001091048, 
                 NM_001097579 
                 Hs.495989 
                 223620_at 
                 7.2 
                 12.6 
                 22.1 
               
               
                   
                 HRH4 
                 59340 
                 NP_001137300, 
                 NM_001143828, 
                 Hs.287388 
                 221170_at 
                 45.8 
                 3.0 
                 45.6 
               
               
                   
                   
                   
                 NP_067637 
                 NM_021624 
               
               
                   
                 IL23R 
                 149233 
                 NP_653302 
                 NM_144701 
                 Hs.677426 
                 1561853_a_at 
                 15.1 
                 7.8 
                 6.2 
               
               
                   
                 IRS2 
                 8660 
                 NP_003740 
                 NM_003749 
                 Hs.442344 
                 209185_s_at 
                 3.3 
                 6.4 
                 5.1 
               
               
                   
                 KCNE3 
                 10008 
                 NP_005463 
                 NM_005472 
                 Hs.523899 
                 227647_at 
                 14.9 
                 5.0 
                 3.7 
               
               
                   
                 L1CAM 
                 3897 
                 NP_000416, 
                 NM_000425, 
                 Hs.522818 
                 204584_at 
                 10.3 
                 6.6 
                 5.9 
               
               
                   
                   
                   
                 NP_076493 
                 NM_024003 
               
               
                   
                 MCAM 
                 4162 
                 NP_006491 
                 NM_006500 
                 Hs.599039 
                 210869_s_at 
                 12.8 
                 24.4 
                 4.3 
               
               
                   
                 MFAP3L 
                 9848 
                 NP_001009554, 
                 NM_001009554, 
                 Hs.593942 
                 205442_at 
                 25.8 
                 22.6 
                 10.5 
               
               
                   
                   
                   
                 NP_067679 
                 NM_021647 
                   
                 210492_at 
                 3.5 
                 4.7 
                 6.7 
               
               
                   
                 MUC20 
                 200958 
                 NP_001091986, 
                 NM_001098516, 
                 Hs.308992 
                 231941_s_at 
                 8.3 
                 3.4 
                 7.2 
               
               
                   
                   
                   
                 NP_689886, 
                 NM_152673, 
               
               
                   
                   
                   
                 XP_001726746 
                 XM_001726694 
               
               
                   
                 MYO7A 
                 4647 
                 NP_000251, 
                 NM_000260, 
                 Hs.370421 
                 208189_s_at 
                 13.7 
                 13.0 
                 6.8 
               
               
                   
                   
                   
                 NP_001120651, 
                 NM_001127179, 
                   
                 211103_at 
                 7.5 
                 15.1 
                 5.1 
               
               
                   
                   
                   
                 NP_001120652 
                 NM_001127180 
               
               
                   
                 POPDC3 
                 64208 
                 NP_071756 
                 NM_022361, 
                 Hs.458336 
                 219926_at 
                 4.5 
                 12.9 
                 12.8 
               
               
                   
                   
                   
                   
                 NR_024539 
               
               
                   
                 PTPRM 
                 5797 
                 NP_001098714, 
                 NM_001105244, 
                 Hs.49774 
                 1555579_s_at 
                 4.1 
                 66.0 
                 4.1 
               
               
                   
                   
                   
                 NP_002836 
                 NM_002845 
               
               
                   
                 SHROOM2 
                 357 
                 NP_001640 
                 NM_001649 
                 Hs.567236 
                 204967_at 
                 11.5 
                 3.5 
                 5.9 
               
               
                   
                 SLC16A4 
                 9122 
                 NP_004687 
                 NM_004696 
                 Hs.351306 
                 205234_at 
                 29.8 
                 16.6 
                 6.8 
               
               
                   
                 SLCO2B1 
                 11309 
                 NP_009187 
                 NM_007256 
                 Hs.7884 
                 203473_at 
                 11.0 
                 5.9 
                 5.9 
               
               
                   
                 SORBS1 
                 10580 
                 NP_001030126, 
                 NM_001034954, 
                 Hs.713556 
                 218087_s_at 
                 37.9 
                 4.7 
                 12.8 
               
               
                   
                   
                   
                 NP_001030127, 
                 NM_001034955, 
                   
                 222513_s_at 
                 14.4 
                 3.6 
                 8.2 
               
               
                   
                   
                   
                 NP_001030128, 
                 NM_001034956, 
               
               
                   
                   
                   
                 NP_001030129, 
                 NM_001034957, 
               
               
                   
                   
                   
                 NP_006425, 
                 NM_006434, 
               
               
                   
                   
                   
                 NP_056200, 
                 NM_015385, 
               
               
                   
                   
                   
                 NP_079267 
                 NM_024991 
               
               
                   
                 TANC1 
                 85461 
                 NP_203752 
                 NM_033394 
                 Hs.61590 
                 225308_s_at 
                 8.1 
                 17.7 
                 4.9 
               
               
                   
                 TANC2 
                 26115 
                 NP_079461 
                 NM_025185 
                 Hs.410889 
                 224952_at 
                 5.3 
                 4.9 
                 6.4 
               
               
                   
                 TJP1 
                 7082 
                 NP_003248, 
                 NM_003257, 
                 Hs.716406 
                 202011_at 
                 11.5 
                 11.7 
                 5.6 
               
               
                   
                   
                   
                 NP_783297 
                 NM_175610 
               
               
                   
                 TMEM163 
                 81615 
                 NP_112185 
                 NM_030923 
                 Hs.369471 
                 1552626_a_at 
                 10.8 
                 12.6 
                 13.9 
               
               
                   
                   
                   
                   
                   
                   
                 223503_at 
                 18.5 
                 23.9 
                 21.7 
               
               
                   
                 TMEM44 
                 93109 
                 NP_001011655, 
                 NM_001011655, 
                 Hs.478729 
                 228054_at 
                 7.4 
                 5.2 
                 3.3 
               
               
                   
                   
                   
                 NP_612408 
                 NM_138399 
               
               
                   
                 TNS3 
                 64759 
                 NP_073585 
                 NM_022748 
                 Hs.520814 
                 217853_at 
                 7.8 
                 27.1 
                 6.4 
               
               
                   
                 UNC13C 
                 440279 
                 NP_001074003 
                 NM_001080534 
                 Hs.657273 
                 1556095_at 
                 7.3 
                 6.1 
                 3.8 
               
               
                   
                 UPK1B 
                 7348 
                 NP_008883 
                 NM_006952 
                 Hs.271580 
                 210065_s_at 
                 5.3 
                 9.6 
                 10.3 
               
               
                   
                 WDFY3 
                 23001 
                 NP_055806, 
                 NM_014991, 
                 Hs.480116 
                 212598_at 
                 10.7 
                 16.1 
                 19.6 
               
               
                   
                   
                   
                 NP_848698, 
                 NM_178583, 
                   
                 212602_at 
                 8.5 
                 19.4 
                 9.8 
               
               
                   
                   
                   
                 NP_848700 
                 NM_178585 
                   
                 212606_at 
                 22.6 
                 62.2 
                 20.5 
               
               
                 Extracellular/ 
                 CXCL13 
                 10563 
                 NP_006410 
                 NM_006419 
                 Hs.100431 
                 205242_at 
                 47.5 
                 40.4 
                 4.8 
               
               
                 secreted 
                 IL17A 
                 3605 
                 NP_002181 
                 NM_002190 
                 Hs.41724 
                 208402_at 
                 16.5 
                 11.1 
                 3.2 
               
               
                   
                   
                   
                   
                   
                   
                 216876_s_at 
                 404.7 
                 50.0 
                 7.6 
               
               
                   
                 IL17F 
                 112744 
                 NP_443104 
                 NM_052872 
                 Hs.272295 
                 234408_at 
                 464.4 
                 421.4 
                 77.1 
               
               
                   
                 IL22 
                 50616 
                 NP_065386 
                 NM_020525 
                 Hs.287369 
                 221165_s_at 
                 4.7 
                 4.6 
                 4.3 
               
               
                   
                   
                   
                   
                   
                   
                 222974_at 
                 4.3 
                 5.5 
                 9.8 
               
               
                   
                 IL26 
                 55801 
                 NP_060872 
                 NM_018402 
                 Hs.272350 
                 221111_at 
                 10.2 
                 22.5 
                 67.8 
               
               
                   
                 IL9 
                 3578 
                 NP_000581 
                 NM_000590 
                 Hs.960 
                 208193_at 
                 729.7 
                 174.0 
                 35.8 
               
               
                   
                 PCOLCE2 
                 26577 
                 NP_037495 
                 NM_013363 
                 Hs.8944 
                 219295_s_at 
                 10.8 
                 19.3 
                 6.2 
               
               
                   
                 PNOC 
                 5368 
                 NP_006219 
                 NM_006228 
                 Hs.88218 
                 205901_at 
                 39.4 
                 11.4 
                 24.3 
               
               
                   
                 SMPDL3A 
                 10924 
                 NP_006705 
                 NM_006714 
                 Hs.486357 
                 213624_at 
                 3.4 
                 3.3 
                 3.5 
               
               
                   
                 TGFBI 
                 7045 
                 NP_000349 
                 NM_000358 
                 Hs.369397 
                 201506_at 
                 55.9 
                 318.3 
                 32.0 
               
               
                 Intracellular 
                 BCAT1 
                 586 
                 NP_005495 
                 NM_005504 
                 Hs.438993 
                 214452_at 
                 3.1 
                 5.8 
                 28.9 
               
               
                   
                 BHLHE22 
                 27319 
                 NP_689627 
                 NM_152414 
                 Hs.591870 
                 228636_at 
                 11.6 
                 14.2 
                 18.7 
               
               
                   
                 C13orf18, 
                 80183, 
                 NP_079389, 
                 NM_025113, 
                 Hs.98117 
                 44790_s_at 
                 3.2 
                 18.8 
                 12.4 
               
               
                   
                 LOC728970 
                 728970 
                 XP_001132115, 
                 XM_001132115, 
               
               
                   
                   
                   
                 XP_001133896, 
                 XM_001133896, 
               
               
                   
                   
                   
                 XP_001720207 
                 XM_001720155 
               
               
                   
                 CA2 
                 760 
                 NP_000058 
                 NM_000067 
                 Hs.155097 
                 209301_at 
                 5.2 
                 61.3 
                 167.6 
               
               
                   
                 CCDC3 
                 83643 
                 NP_113643 
                 NM_031455 
                 Hs.498720 
                 223316_at 
                 11.2 
                 52.3 
                 43.4 
               
               
                   
                 CDS1 
                 1040 
                 NP_001254 
                 NM_001263 
                 Hs.654899 
                 205709_s_at 
                 7.3 
                 9.5 
                 4.2 
               
               
                   
                   
                   
                   
                   
                   
                 226185_at 
                 4.2 
                 7.8 
                 3.3 
               
               
                   
                 CHN1 
                 1123 
                 NP_001020372, 
                 NM_001025201, 
                 Hs.654534 
                 212624_s_at 
                 11.5 
                 21.3 
                 9.1 
               
               
                   
                   
                   
                 NP_001813 
                 NM_001822 
               
               
                   
                 CLIC5, 
                 53405, 
                 NP_001107558, 
                 NM_001114086, 
                 Hs.485489 
                 213317_at 
                 7.1 
                 22.1 
                 9.6 
               
               
                   
                 LOC100131610 
                 100131610 
                 NP_058625, 
                 NM_016929, 
                   
                 217628_at 
                 3.1 
                 4.2 
                 4.6 
               
               
                   
                   
                   
                 XP_001723610 
                 XM_001723558 
                   
                 243917_at 
                 10.8 
                 17.2 
                 11.7 
               
               
                   
                   
                   
                   
                   
                   
                 219866_at 
                 6.2 
                 10.6 
                 12.2 
               
               
                   
                 CTSH 
                 1512 
                 NP_004381, 
                 NM_004390, 
                 Hs.148641 
                 202295_s_at 
                 4.6 
                 12.1 
                 6.9 
               
               
                   
                   
                   
                 NP_683880 
                 NM_148979 
               
               
                   
                 CYP7B1 
                 9420 
                 NP_004811 
                 NM_004820 
                 Hs.667720 
                 207386_at 
                 16.4 
                 11.8 
                 5.3 
               
               
                   
                 DAPK2 
                 23604 
                 NP_055141 
                 NM_014326 
                 Hs.237886 
                 206324_s_at 
                 4.4 
                 4.7 
                 3.9 
               
               
                   
                 DMRT1 
                 1761 
                 NP_068770 
                 NM_021951 
                 Hs.98586 
                 220493_at 
                 5.2 
                 18.4 
                 3.9 
               
               
                   
                 DSE 
                 29940 
                 NP_001074445, 
                 NM_001080976, 
                 Hs.486292 
                 218854_at 
                 15.0 
                 51.2 
                 22.3 
               
               
                   
                   
                   
                 NP_037484 
                 NM_013352 
               
               
                   
                 EML1 
                 2009 
                 NP_001008707, 
                 NM_001008707, 
                 Hs.12451 
                 204796_at 
                 10.1 
                 8.9 
                 5.8 
               
               
                   
                   
                   
                 NP_004425 
                 NM_004434 
                   
                 204797_s_at 
                 3.1 
                 3.1 
                 3.2 
               
               
                   
                 FBXL17 
                 64839 
                 NP_073735 
                 NM_022824 
                 Hs.657225 
                 227203_at 
                 12.6 
                 11.8 
                 4.5 
               
               
                   
                 FBXL21 
                 26223 
                 NP_036291 
                 NM_012159 
                 Hs.591275 
                 1555412_at 
                 26.5 
                 35.3 
                 22.3 
               
               
                   
                 FHOD3 
                 80206 
                 NP_079411 
                 NM_025135 
                 Hs.436636 
                 218980_at 
                 7.0 
                 9.9 
                 6.7 
               
               
                   
                 H2AFY2 
                 55506 
                 NP_061119 
                 NM_018649 
                 Hs.499953 
                 218445_at 
                 3.9 
                 8.2 
                 4.7 
               
               
                   
                 HIST1H2BC 
                 8347 
                 NP_003517 
                 NM_003526 
                 Hs.658713 
                 236193_at 
                 3.8 
                 4.4 
                 3.3 
               
               
                   
                 HLX 
                 3142 
                 NP_068777 
                 NM_021958 
                 Hs.74870 
                 214438_at 
                 3.3 
                 5.2 
                 39.3 
               
               
                   
                 IRAK3 
                 11213 
                 NP_001135995, 
                 NM_001142523, 
                 Hs.369265 
                 213817_at 
                 9.4 
                 18.8 
                 6.5 
               
               
                   
                   
                   
                 NP_009130 
                 NM_007199 
               
               
                   
                 MACC1 
                 346389 
                 NP_877439 
                 NM_182762 
                 Hs.598388 
                 1566764_at 
                 5.6 
                 12.8 
                 3.5 
               
               
                   
                   
                   
                   
                   
                   
                 1566766_a_at 
                 9.2 
                 17.3 
                 4.7 
               
               
                   
                 MAML3 
                 55534 
                 NP_061187 
                 NM_018717 
                 Hs.586165 
                 242794_at 
                 6.4 
                 5.7 
                 4.6 
               
               
                   
                 MAP3K4 
                 4216 
                 NP_005913, 
                 NM_005922, 
                 Hs.390428 
                 204089_x_at 
                 3.3 
                 3.3 
                 3.4 
               
               
                   
                   
                   
                 NP_006715 
                 NM_006724 
                   
                 216199_s_at 
                 3.2 
                 3.6 
                 3.4 
               
               
                   
                 MYO10 
                 4651 
                 NP_036466 
                 NM_012334 
                 Hs.481720 
                 1554026_a_at 
                 9.1 
                 11.7 
                 7.1 
               
               
                   
                   
                   
                   
                   
                   
                 201976_s_at 
                 45.4 
                 19.1 
                 15.0 
               
               
                   
                   
                   
                   
                   
                   
                 216222_s_at 
                 3.0 
                 6.2 
                 6.7 
               
               
                   
                 OTUB2 
                 78990 
                 NP_075601 
                 NM_023112 
                 Hs.278815 
                 219369_s_at 
                 3.1 
                 3.4 
                 3.8 
               
               
                   
                   
                   
                   
                   
                   
                 222878_s_at 
                 4.2 
                 7.2 
                 4.8 
               
               
                   
                 PAPSS2 
                 9060 
                 NP_001015880, 
                 NM_001015880, 
                 Hs.524491 
                 203058_s_at 
                 5.5 
                 11.0 
                 11.1 
               
               
                   
                   
                   
                 NP_004661 
                 NM_004670 
                   
                 203060_s_at 
                 6.3 
                 47.2 
                 17.3 
               
               
                   
                 PCBP3 
                 54039 
                 NP_001123613, 
                 NM_001130141, 
                 Hs.474049 
                 230486_at 
                 4.5 
                 3.1 
                 5.0 
               
               
                   
                   
                   
                 NP_065389 
                 NM_020528 
               
               
                   
                 PDE4DIP 
                 9659 
                 NP_001002810, 
                 NM_001002810, 
                 Hs.654651 
                 205872_x_at 
                 5.2 
                 33.6 
                 4.3 
               
               
                   
                   
                   
                 NP_001002811, 
                 NM_001002811, 
                 Hs.613082 
                 209700_x_at 
                 4.9 
                 29.1 
                 8.3 
               
               
                   
                   
                   
                 NP_001002812, 
                 NM_001002812, 
               
               
                   
                   
                   
                 NP_055459, 
                 NM_014644, 
               
               
                   
                   
                   
                 NP_071754 
                 NM_022359 
               
               
                   
                 PDK4 
                 5166 
                 NP_002603 
                 NM_002612 
                 Hs.8364 
                 225207_at 
                 5.3 
                 3.0 
                 4.1 
               
               
                   
                 PLD1 
                 5337 
                 NP_001123553, 
                 NM_001130081, 
                 Hs.382865 
                 226636_at 
                 3.7 
                 3.2 
                 8.2 
               
               
                   
                   
                   
                 NP_002653 
                 NM_002662 
               
               
                   
                 PPARG 
                 5468 
                 NP_005028, 
                 NM_005037, 
                 Hs.162646 
                 208510_s_at 
                 8.0 
                 22.8 
                 14.1 
               
               
                   
                   
                   
                 NP_056953, 
                 NM_015869, 
               
               
                   
                   
                   
                 NP_619725, 
                 NM_138711, 
               
               
                   
                   
                   
                 NP_619726 
                 NM_138712 
               
               
                   
                 PTPN13 
                 5783 
                 NP_006255, 
                 NM_006264, 
                 Hs.436142 
                 204201_s_at 
                 3.1 
                 4.5 
                 19.7 
               
               
                   
                   
                   
                 NP_542414, 
                 NM_080683, 
                   
                 243792_x_at 
                 7.9 
                 5.5 
                 11.7 
               
               
                   
                   
                   
                 NP_542415, 
                 NM_080684, 
               
               
                   
                   
                   
                 NP_542416 
                 NM_080685 
               
               
                   
                 RGS18 
                 64407 
                 NP_570138 
                 NM_130782 
                 Hs.440890 
                 223809_at 
                 4.1 
                 4.9 
                 3.4 
               
               
                   
                 RGS2 
                 5997 
                 NP_002914 
                 NM_002923 
                 Hs.78944 
                 202388_at 
                 3.3 
                 3.5 
                 8.1 
               
               
                   
                 RGS20 
                 8601 
                 NP_003693, 
                 NM_003702, 
                 Hs.368733 
                 210138_at 
                 6.4 
                 4.9 
                 9.7 
               
               
                   
                   
                   
                 NP_733466 
                 NM_170587 
               
               
                   
                 RORC 
                 6097 
                 NP_001001523, 
                 NM_001001523, 
                 Hs.256022 
                 228806_at 
                 150.1 
                 51.2 
                 5.7 
               
               
                   
                   
                   
                 NP_005051 
                 NM_005060 
               
               
                   
                 SIM1 
                 6492 
                 NP_005059 
                 NM_005068 
                 Hs.520293 
                 1556300_s_at 
                 14.5 
                 5.8 
                 99.6 
               
               
                   
                   
                   
                   
                   
                   
                 206876_at 
                 10.9 
                 5.2 
                 26.9 
               
               
                   
                 SNAI2 
                 6591 
                 NP_003059 
                 NM_003068 
                 Hs.360174 
                 213139_at 
                 8.2 
                 15.0 
                 6.8 
               
               
                   
                 SOX2 
                 6657 
                 NP_003097 
                 NM_003106 
                 Hs.518438 
                 228038_at 
                 14.4 
                 14.4 
                 16.4 
               
               
                   
                 SPIRE1 
                 56907 
                 NP_001122098, 
                 NM_001128626, 
                 Hs.515283 
                 1554807_a_at 
                 6.0 
                 3.3 
                 4.4 
               
               
                   
                   
                   
                 NP_001122099, 
                 NM_001128627, 
                   
                 224995_at 
                 7.2 
                 5.2 
                 5.9 
               
               
                   
                   
                   
                 NP_064533 
                 NM_020148 
                   
                 225018_at 
                 5.5 
                 5.4 
                 7.8 
               
               
                   
                 TBC1D12 
                 23232 
                 NP_056003 
                 NM_015188 
                 Hs.500598 
                 221858_at 
                 4.2 
                 3.2 
                 3.1 
               
               
                   
                 TGM5 
                 9333 
                 NP_004236, 
                 NM_004245, 
                 Hs.129719 
                 207911_s_at 
                 5.1 
                 7.7 
                 6.5 
               
               
                   
                   
                   
                 NP_963925 
                 NM_201631 
               
               
                   
                 TMOD1 
                 7111 
                 NP_003266 
                 NM_003275 
                 Hs.494595 
                 203661_s_at 
                 6.2 
                 10.7 
                 4.0 
               
               
                   
                   
                   
                   
                   
                   
                 203662_s_at 
                 6.2 
                 9.5 
                 3.7 
               
               
                   
                 TUBB6 
                 84617 
                 NP_115914 
                 NM_032525 
                 Hs.193491 
                 209191_at 
                 3.5 
                 11.2 
                 6.4 
               
               
                 Unknown 
                 C12orf64 
                 283310 
                 NP_775862 
                 NM_173591 
                 Hs.355145 
                 1553746_a_at 
                 4.2 
                 5.3 
                 10.8 
               
               
                   
                 C6orf168 
                 84553 
                 NP_115900 
                 NM_032511 
                 Hs.573245 
                 232067_at 
                 3.3 
                 5.8 
                 37.1 
               
               
                   
                 CAMSAP1L1 
                 23271 
                 NP_982284 
                 NM_203459 
                 Hs.23585 
                 217196_s_at 
                 22.5 
                 10.1 
                 3.7 
               
               
                   
                 MAGED4, 
                 728239, 
                 NP_001092270, 
                 NM_001098800, 
                 Hs.571729 
                 223313_s_at 
                 16.3 
                 8.6 
                 3.5 
               
               
                   
                 MAGED4B 
                 81557 
                 NP_110428, 
                 NM_030801, 
               
               
                   
                   
                   
                 NP_803879, 
                 NM_177535, 
               
               
                   
                   
                   
                 NP_803881 
                 NM_177537 
               
               
                   
                 — 
                 — 
                 — 
                 AK093612 
                 Hs.663643 
                 1556602_at 
                 4.1 
                 5.9 
                 6.3 
               
               
                   
                 — 
                 — 
                 — 
                 BC010059 
                 Hs.637648 
                 1562957_at 
                 6.6 
                 3.6 
                 4.6 
               
               
                   
                 — 
                 — 
                 — 
                 AK055628, 
                 Hs.594351 
                 226777_at 
                 30.4 
                 42.8 
                 3.4 
               
               
                   
                   
                   
                   
                 uc001ljj.1 
               
               
                   
                 — 
                 — 
                 — 
                 GENSCAN00000030683 
                 — 
                 227985_at 
                 13.4 
                 19.2 
                 3.6 
               
               
                   
                 — 
                 — 
                 — 
                 AA416573, 
                 Hs.654918 
                 229951_x_at 
                 4.2 
                 13.5 
                 4.9 
               
               
                   
                   
                   
                   
                 AA628762, 
               
               
                   
                   
                   
                   
                 D53835, 
               
               
                   
                   
                   
                   
                 D53836, 
               
               
                   
                   
                   
                   
                 H24473, 
               
               
                   
                   
                   
                   
                 R37871, 
               
               
                   
                   
                   
                   
                 R40232, 
               
               
                   
                   
                   
                   
                 T10348, 
               
               
                   
                   
                   
                   
                 T23451, 
               
               
                   
                   
                   
                   
                 W56351, 
               
               
                   
                   
                   
                   
                 W57867, 
               
               
                   
                   
                   
                   
                 Z28733 
               
               
                   
                 — 
                 — 
                 — 
                 AK027107 
                 Hs.655798 
                 232331_at 
                 3.5 
                 3.5 
                 9.0 
               
               
                   
                 — 
                 — 
                 — 
                 AI269134, 
                 Hs.657330 
                 235438_at 
                 73.9 
                 22.0 
                 3.3 
               
               
                   
                   
                   
                   
                 AI312873, 
               
               
                   
                   
                   
                   
                 AI671475, 
               
               
                   
                   
                   
                   
                 AV656012, 
               
               
                   
                   
                   
                   
                 AW162011, 
               
               
                   
                   
                   
                   
                 BG151392, 
               
               
                   
                   
                   
                   
                 H69527, 
               
               
                   
                   
                   
                   
                 N43169, 
               
               
                   
                   
                   
                   
                 Z36958 
               
               
                   
                 — 
                 — 
                 — 
                 AA687415, 
                 Hs.434948 
                 238009_at 
                 4.6 
                 15.9 
                 15.0 
               
               
                   
                   
                   
                   
                 AA96901, 
               
               
                   
                   
                   
                   
                 AI291640, 
               
               
                   
                   
                   
                   
                 AI446064, 
               
               
                   
                   
                   
                   
                 AI634557, 
               
               
                   
                   
                   
                   
                 AI694948, 
               
               
                   
                   
                   
                   
                 AI701854, 
               
               
                   
                   
                   
                   
                 AI983938, 
               
               
                   
                   
                   
                   
                 AV745212, 
               
               
                   
                   
                   
                   
                 AV745909, 
               
               
                   
                   
                   
                   
                 AV746001, 
               
               
                   
                   
                   
                   
                 AW008696, 
               
               
                   
                   
                   
                   
                 AW511701, 
               
               
                   
                   
                   
                   
                 AW974416, 
               
               
                   
                   
                   
                   
                 BG149302, 
               
               
                   
                   
                   
                   
                 BG150103, 
               
               
                   
                   
                   
                   
                 N66771, 
               
               
                   
                   
                   
                   
                 R66991 
               
               
                   
                 — 
                 — 
                 — 
                 AI148241, 
                 Hs.659083 
                 238151_at 
                 37.6 
                 48.1 
                 29.9 
               
               
                   
                   
                   
                   
                 AI735444, 
               
               
                   
                   
                   
                   
                 BE645654, 
               
               
                   
                   
                   
                   
                 BF510855, 
               
               
                   
                   
                   
                   
                 BF511636 
               
               
                   
                 — 
                 — 
                 — 
                 AK094629 
                 Hs.594896 
                 238623_at 
                 7.0 
                 5.6 
                 6.8 
               
               
                   
                 — 
                 — 
                 — 
                 AI435469, 
                 Hs.656932 
                 241022_at 
                 6.1 
                 10.7 
                 12.4 
               
               
                   
                   
                   
                   
                 BF111679, 
               
               
                   
                   
                   
                   
                 BF112253, 
               
               
                   
                   
                   
                   
                 R37814 
               
               
                   
                 — 
                 — 
                 — 
                 AA846423, 
                 Hs.665895 
                 243922_at 
                 16.7 
                 12.8 
                 6.0 
               
               
                   
                   
                   
                   
                 AI022103, 
               
               
                   
                   
                   
                   
                 BF061333 
               
               
                   
                 — 
                 — 
                 — 
                 AA648972, 
                 Hs.602350 
                 244247_at 
                 3.9 
                 3.4 
                 5.3 
               
               
                   
                   
                   
                   
                 AA879467, 
               
               
                   
                   
                   
                   
                 AI802768, 
               
               
                   
                   
                   
                   
                 AW974600 
               
               
                   
               
            
           
         
       
     
     Among the above genes, those shown in Table 8 have been known for their specific expression in Th17 cells. 
     
       
         
           
               
               
               
             
               
                 TABLE 8 
               
             
            
               
                   
               
               
                 SEQ 
                   
                 Expression ratio 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 ID 
                 Gene symbol 
                 Entrez 
                 Protein 
                 Transcript 
                 UniGene 
                 Probe Set 
                 Th17/ 
                   
                   
               
               
                 NO: 
                 (Gene title) 
                 Gene ID 
                 ID 
                 ID 
                 ID 
                 ID 
                 Th1 
                 Th17/Th2 
                 Th17/Treg 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 175 
                 IL23R(interleukin 23 receptor) 
                 149233 
                 NP_653302 
                 NM_144701 
                 Hs.677426 
                 1552912_a_at 
                 7.6 
                 11.7 
                 4.5 
               
               
                 176 
                 IL17A(interleukin 17A) 
                 3605 
                 NP_002181 
                 NM_002190 
                 Hs.41724 
                 216876_s_at 
                 397.5 
                 473.0 
                 29.3 
               
               
                 177 
                 IL17F(interleukin 17F) 
                 112744 
                 NP_443104 
                 NM_052872 
                 Hs.272295 
                 234408_at 
                 611.6 
                 951.0 
                 383.6 
               
               
                 178 
                 IL22(interleukin 22) 
                 50616 
                 NP_065386 
                 NM_020525 
                 Hs.287369 
                 222974_at 
                 6.4 
                 29.9 
                 10.6 
               
               
                 179 
                 IL26(interleukin 26) 
                 55801 
                 NP_060872 
                 NM_018402 
                 Hs.272350 
                 221111_at 
                 10.1 
                 13.0 
                 39.4 
               
               
                 180 
                 RORC(RAR-related 
                 6097 
                 NP_001001523, 
                 NM_001001523, 
                 Hs.256022 
                 228806_at 
                 13.8 
                 174.9 
                 7.6 
               
               
                   
                 orphan receptor C) 
                   
                 NP_005051 
                 NM_005060 
               
               
                   
               
            
           
         
       
     
     Expression levels of those known genes in Th1, Th2, Treg and Th17 cells obtained in the above step 2. were analyzed with microarray as described above. It was found that those genes were expressed 4 to 950 times higher in Th17 cells than in Th1, Th2 and Treg cells. These results are shown in  FIG. 1 . These results indicated that the above cells are suitable for investigation of markers for detecting Th17 cells. 
     The present inventors have identified novel polynucleotide markers for detecting Th17 cells by excluding the genes shown in Table 8 from those obtained as above. These novel polynucleotide markers are shown in Table 9. 
     In this table, “Condition” means with or without activation stimulation of cells. The genes designated as “Common” in the column of “Condition” are the genes specifically expressed in both Th17 cells with stimulation and without stimulation. The genes designated as “With stimulation” and “Without stimulation” are the genes specifically expressed either in Th17 cells with stimulation or without stimulation, respectively. 
     
       
         
           
               
               
               
               
               
               
               
               
               
               
             
               
                 TABLE 9 
               
               
                   
               
               
                 Location of 
                   
                   
                   
                   
                   
                   
                   
                   
                 SEQ 
               
               
                 encoded 
                   
                   
                   
                 Entrez 
                 Protein 
                 Transcript 
                 UniGene 
                 Probe Set 
                 ID 
               
               
                 protein 
                 Condition 
                 No. 
                 Gene symbol 
                 Gene ID 
                 ID 
                 ID 
                 ID 
                 ID 
                 NO: 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Membrane 
                 Common 
                 1 
                 ADAM12 
                 8038 
                 NP_003465, 
                 NM_003474, 
                 Hs.594537 
                 202952_s_at 
                 1 
               
               
                   
                   
                   
                   
                   
                 NP_067673 
                 NM_021641 
               
               
                   
                   
                 2 
                 ANKS1B 
                 56899 
                 NP_064525, 
                 NM_020140, 
                 Hs.506458 
                 227439_at 
                 2 
               
               
                   
                   
                   
                   
                   
                 NP_690001, 
                 NM_152788, 
                   
                 240292_x_at 
                 3 
               
               
                   
                   
                   
                   
                   
                 NP_858056 
                 NM_181670 
               
               
                   
                   
                 3 
                 ATP6V0A4 
                 50617 
                 NP_065683, 
                 NM_020632, 
                 Hs.98967 
                 220197_at 
                 4 
               
               
                   
                   
                   
                   
                   
                 NP_570855, 
                 NM_130840, 
               
               
                   
                   
                   
                   
                   
                 NP_570856 
                 NM_130841 
               
               
                   
                   
                 4 
                 ATP9A 
                 10079 
                 NP_006036 
                 NM_006045 
                 Hs.714307 
                 212062_at 
                 5 
               
               
                   
                   
                 5 
                 BVES 
                 11149 
                 NP_009004, 
                 NM_007073, 
                 Hs.221660 
                 228783_at 
                 6 
               
               
                   
                   
                   
                   
                   
                 NP_671488 
                 NM_147147 
               
               
                   
                   
                 6 
                 C5orf40 
                 408263 
                 NP_001001343 
                 NM_001001343 
                 Hs.437066 
                 1554801_at 
                 7 
               
               
                   
                   
                 7 
                 CDH4 
                 1002 
                 NP_001785 
                 NM_001794 
                 Hs.473231 
                 206866_at 
                 8 
               
               
                   
                   
                 8 
                 DIO2 
                 1734 
                 NP_000784, 
                 NM_000793, 
                 Hs.202354 
                 203700_s_at 
                 9 
               
               
                   
                   
                   
                   
                   
                 NP_001007024, 
                 NM_001007023, 
               
               
                   
                   
                   
                   
                   
                 NP_054644 
                 NM_013989 
               
               
                   
                   
                 9 
                 DMD 
                 1756 
                 NP_000100, 
                 NM_000109, 
                 Hs.495912 
                 203881_s_at 
                 10 
               
               
                   
                   
                   
                   
                   
                 NP_003997, 
                 NM_004006, 
               
               
                   
                   
                   
                   
                   
                 NP_003998, 
                 NM_004007, 
               
               
                   
                   
                   
                   
                   
                 NP_004000, 
                 NM_004009, 
               
               
                   
                   
                   
                   
                   
                 NP_004001, 
                 NM_004010, 
               
               
                   
                   
                   
                   
                   
                 NP_004002, 
                 NM_004011, 
               
               
                   
                   
                   
                   
                   
                 NP_004003, 
                 NM_004012, 
               
               
                   
                   
                   
                   
                   
                 NP_004004, 
                 NM_004013, 
               
               
                   
                   
                   
                   
                   
                 NP_004005, 
                 NM_004014, 
               
               
                   
                   
                   
                   
                   
                 NP_004006, 
                 NM_004015, 
               
               
                   
                   
                   
                   
                   
                 NP_004007, 
                 NM_004016, 
               
               
                   
                   
                   
                   
                   
                 NP_004008, 
                 NM_004017, 
               
               
                   
                   
                   
                   
                   
                 NP_004009, 
                 NM_004018, 
               
               
                   
                   
                   
                   
                   
                 NP_004010, 
                 NM_004019, 
               
               
                   
                   
                   
                   
                   
                 NP_004011, 
                 NM_004020, 
               
               
                   
                   
                   
                   
                   
                 NP_004012, 
                 NM_004021, 
               
               
                   
                   
                   
                   
                   
                 NP_004013, 
                 NM_004022, 
               
               
                   
                   
                   
                   
                   
                 NP_004014 
                 NM_004023 
               
               
                   
                   
                 10 
                 GPR34 
                 2857 
                 NP_001091048, 
                 NM_001097579, 
                 Hs.495989 
                 223620_at 
                 11 
               
               
                   
                   
                   
                   
                   
                 NP_005291 
                 NM_005300 
               
               
                   
                   
                 11 
                 IRS2 
                 8660 
                 NP_003740 
                 NM_003749 
                 Hs.442344 
                 209184_s_at 
                 12 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 209185_s_at 
                 13 
               
               
                   
                   
                 12 
                 KCNE3 
                 10008 
                 NP_005463 
                 NM_005472 
                 Hs.523899 
                 227647_at 
                 14 
               
               
                   
                   
                 13 
                 L1CAM 
                 3897 
                 NP_000416, 
                 NM_000425, 
                 Hs.522818 
                 204584_at 
                 15 
               
               
                   
                   
                   
                   
                   
                 NP_076493 
                 NM_024003 
               
               
                   
                   
                 14 
                 MCAM 
                 4162 
                 NP_006491 
                 NM_006500 
                 Hs.599039 
                 210869_s_at 
                 16 
               
               
                   
                   
                 15 
                 MFAP3L 
                 9848 
                 NP_001009554, 
                 NM_001009554, 
                 Hs.593942 
                 205442_at 
                 17 
               
               
                   
                   
                   
                   
                   
                 NP_067679 
                 NM_021647 
               
               
                   
                   
                 16 
                 MYO7A 
                 4647 
                 NP_000251, 
                 NM_00260, 
                 Hs.370421 
                 208189_s_at 
                 18 
               
               
                   
                   
                   
                   
                   
                 NP_001120651, 
                 NM_001127179, 
               
               
                   
                   
                   
                   
                   
                 NP_001120652 
                 NM_001127180 
               
               
                   
                   
                 17 
                 PTPRM 
                 5797 
                 NP_001098714, 
                 NM_001105244, 
                 Hs.49774 
                 1555579_s_at 
                 19 
               
               
                   
                   
                   
                   
                   
                 NP_002836 
                 NM_002845 
               
               
                   
                   
                 18 
                 SHROOM2 
                 357 
                 NP_001640 
                 NM_001649 
                 Hs.567236 
                 204967_at 
                 20 
               
               
                   
                   
                 19 
                 SLC16A4 
                 9122 
                 NP_004687 
                 NM_004696 
                 Hs.351306 
                 205234_at 
                 21 
               
               
                   
                   
                 20 
                 SLCO2B1 
                 11309 
                 NP_009187 
                 NM_007256 
                 Hs.7884 
                 203473_at 
                 22 
               
               
                   
                   
                 21 
                 TANC2 
                 26115 
                 NP_079461 
                 NM_025185 
                 Hs.410889 
                 208425_s_at 
                 23 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 224952_at 
                 24 
               
               
                   
                   
                 22 
                 TJP1 
                 7082 
                 NP_003248, 
                 NM_003257, 
                 Hs.716406 
                 202011_at 
                 25 
               
               
                   
                   
                   
                   
                   
                 NP_783297 
                 NM_175610 
               
               
                   
                   
                 23 
                 TMEM163 
                 81615 
                 NP_112185 
                 NM_030923 
                 Hs.369471 
                 1552626_a_at 
                 26 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 223503_at 
                 27 
               
               
                   
                   
                 24 
                 TNS3 
                 64759 
                 NP_073585 
                 NM_022748 
                 Hs.520814 
                 217853_at 
                 28 
               
               
                   
                   
                 25 
                 UPK1B 
                 7348 
                 NP_008883 
                 NM_006952 
                 Hs.271580 
                 210065_s_at 
                 29 
               
               
                   
                   
                 26 
                 WDFY3 
                 23001 
                 NP_055806, 
                 NM_014991, 
                 Hs.480116 
                 212598_at 
                 30 
               
               
                   
                   
                   
                   
                   
                 NP_848698, 
                 NM_178583, 
                   
                 212602_at 
                 31 
               
               
                   
                   
                   
                   
                   
                 NP_848700 
                 NM_178585 
                   
                 212606_at 
                 32 
               
               
                   
                 w/o 
                 27 
                 DRD2 
                 1813 
                 NP_000786, 
                 NM_000795, 
                 Hs.73893 
                 216938_x_at 
                 33 
               
               
                   
                 stimulation 
                   
                   
                   
                 NP_057658 
                 NM_016574 
               
               
                   
                   
                 28 
                 GJC1 
                 10052 
                 NP_001073852, 
                 NM_001080383, 
                 Hs.532593 
                 228776_at 
                 34 
               
               
                   
                   
                   
                   
                   
                 NP_005488 
                 NM_005497 
                   
                 243502_at 
                 35 
               
               
                   
                 Without 
                 29 
                 PGBD5, 
                 79605, 
                 NP_078830, 
                 NM_024554, 
                 Hs.520463 
                 219225_at 
                 36 
               
               
                   
                 stimulation 
                   
                 LOC100134440 
                 100134440 
                 XP_001716155 
                 XM_001716103 
               
               
                   
                   
                 30 
                 MS4A7 
                 58475 
                 NP_067024, 
                 NM_021201, 
                 Hs.530735 
                 223343_at 
                 37 
               
               
                   
                   
                   
                   
                   
                 NP_996821, 
                 NM_206938, 
               
               
                   
                   
                   
                   
                   
                 NP_996822, 
                 NM_206939, 
               
               
                   
                   
                   
                   
                   
                 NP_996823 
                 NM_206940 
               
               
                   
                   
                 31 
                 ODZ4 
                 26011 
                 NP_001092286 
                 NM_001098816 
                 Hs.213087 
                 213273_at 
                 38 
               
               
                   
                   
                 32 
                 PHKA1 
                 5255 
                 NP_001116142, 
                 NM_001122670, 
                 Hs.201379 
                 229876_at 
                 39 
               
               
                   
                   
                   
                   
                   
                 NP_002628 
                 NM_002637 
               
               
                   
                   
                 33 
                 RGS1 
                 5996 
                 NP_002913 
                 NM_002922 
                 Hs.75256 
                 202988_s_at 
                 40 
               
               
                   
                   
                 34 
                 SHB 
                 6461 
                 NP_003019 
                 NM_003028 
                 Hs.521482 
                 1557458_s_at 
                 41 
               
               
                   
                   
                 35 
                 SLC44A3 
                 126969 
                 NP_001107578, 
                 NM_001114106, 
                 Hs.483423 
                 228221_at 
                 42 
               
               
                   
                   
                   
                   
                   
                 NP_689582 
                 NM_152369 
               
               
                   
                   
                 36 
                 SLC6A15 
                 55117 
                 NP_060527, 
                 NM_018057, 
                 Hs.44424 
                 206376_at 
                 43 
               
               
                   
                   
                   
                   
                   
                 NP_877499 
                 NM_182767 
               
               
                   
                   
                 37 
                 SYNGR3 
                 9143 
                 NP_004200 
                 NM_004209 
                 Hs.435277 
                 205691_at 
                 44 
               
               
                   
                 With 
                 38 
                 AKAP12 
                 9590 
                 NP_005091, 
                 NM_005100, 
                 Hs.371240 
                 210517_s_at 
                 45 
               
               
                   
                 stimulation 
                   
                   
                   
                 NP_653080 
                 NM_144497 
                   
                 227529_s_at 
                 46 
               
               
                   
                   
                 39 
                 C9orf125 
                 84302 
                 NP_115718 
                 NM_032342 
                 Hs.655738 
                 224458_at 
                 47 
               
               
                   
                   
                 40 
                 DPY19L2 
                 283417 
                 NP_776173 
                 NM_173812 
                 Hs.533644 
                 230158_at 
                 48 
               
               
                   
                   
                 41 
                 HRH4 
                 59340 
                 NP_001137300, 
                 NM_001143828, 
                 Hs.287388 
                 221170_at 
                 49 
               
               
                   
                   
                   
                   
                   
                 NP_067637 
                 NM_021624 
               
               
                   
                   
                 42 
                 MUC20 
                 200958 
                 NP_001091986, 
                 NM_001098516, 
                 Hs.308992 
                 231941_s_at 
                 50 
               
               
                   
                   
                   
                   
                   
                 NP_689886, 
                 NM_152673, 
               
               
                   
                   
                   
                   
                   
                 XP_001726746 
                 XM_001726694 
               
               
                   
                   
                 43 
                 POPDC3 
                 64208 
                 NP_071756 
                 NM_022361, 
                 Hs.458336 
                 219926_at 
                 51 
               
               
                   
                   
                   
                   
                   
                   
                 NR_024539 
               
               
                   
                   
                 44 
                 SORBS1 
                 10580 
                 NP_001030126, 
                 NM_001034954, 
                 Hs.713556 
                 218087_s_at 
                 52 
               
               
                   
                   
                   
                   
                   
                 NP_001030127, 
                 NM_001034955, 
                   
                 222513_s_at 
                 53 
               
               
                   
                   
                   
                   
                   
                 NP_001030128, 
                 NM_001034956, 
               
               
                   
                   
                   
                   
                   
                 NP_001030129, 
                 NM_001034957, 
               
               
                   
                   
                   
                   
                   
                 NP_006425, 
                 NM_006434, 
               
               
                   
                   
                   
                   
                   
                 NP_056200, 
                 NM_015385, 
               
               
                   
                   
                   
                   
                   
                 NP_079267 
                 NM_024991 
               
               
                   
                   
                 45 
                 TANC1 
                 85461 
                 NP_203752 
                 NM_033394 
                 Hs.61590 
                 225308_s_at 
                 54 
               
               
                   
                   
                 46 
                 TMEM44 
                 93109 
                 NP_001011655, 
                 NM_001011655, 
                 Hs.478729 
                 228054_at 
                 55 
               
               
                   
                   
                   
                   
                   
                 NP_612408 
                 NM_138399 
               
               
                   
                   
                 47 
                 UNC13C 
                 440279 
                 NP_001074003 
                 NM_001080534 
                 Hs.657273 
                 1556095_at 
                 56 
               
               
                 Extra- 
                 Common 
                 48 
                 CXCL13 
                 10563 
                 NP_006410 
                 NM_006419 
                 Hs.100431 
                 205242_at 
                 57 
               
               
                 cellular/ 
                   
                 49 
                 IL9 
                 3578 
                 NP_000581 
                 NM_000590 
                 Hs.960 
                 208193_at 
                 58 
               
               
                 secreted 
                   
                 50 
                 PCOLCE2 
                 26577 
                 NP_037495 
                 NM_013363 
                 Hs.8944 
                 219295_s_at 
                 59 
               
               
                   
                   
                 51 
                 PNOC 
                 5368 
                 NP_006219 
                 NM_006228 
                 Hs.88218 
                 205901_at 
                 60 
               
               
                   
                   
                 52 
                 SMPDL3A 
                 10924 
                 NP_006705 
                 NM_006714 
                 Hs.486357 
                 213624_at 
                 61 
               
               
                   
                   
                 53 
                 TGFBI 
                 7045 
                 NP_000349 
                 NM_000358 
                 Hs.369397 
                 201506_at 
                 62 
               
               
                   
                 w/o 
                 54 
                 C17orf99 
                 100141515 
                 NP_001156547 
                 NM_001163075 
                 Hs.633034 
                 236981_at 
                 63 
               
               
                   
                 stimulation 
                 55 
                 EBI3 
                 10148 
                 NP_005746 
                 NM_005755 
                 Hs.501452 
                 219424_at 
                 64 
               
               
                   
                   
                 56 
                 IL1A 
                 3552 
                 NP_000566 
                 NM_000575 
                 Hs.1722 
                 210118_s_at 
                 65 
               
               
                   
                   
                 57 
                 WNT3 
                 7473 
                 NP_110380 
                 NM_030753 
                 Hs.445884 
                 229103_at 
                 66 
               
               
                 Intracellular 
                 Common 
                 58 
                 BCAT1 
                 586 
                 NP_005495 
                 NM_005504 
                 Hs.438993 
                 214390_s_at 
                 67 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 214452_at 
                 68 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 225285_at 
                 69 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 226517_at 
                 70 
               
               
                   
                   
                 59 
                 BHLHE22 
                 27319 
                 NP_689627 
                 NM_152414 
                 Hs.591870 
                 228636_at 
                 71 
               
               
                   
                   
                 60 
                 C13orf18, 
                 80183, 
                 NP_079389, 
                 NM_025113, 
                 Hs.98117 
                 44790_s_at 
                 72 
               
               
                   
                   
                   
                 LOC728970 
                 728970 
                 XP_001132115, 
                 XM_001132115, 
               
               
                   
                   
                   
                   
                   
                 XP_001133896, 
                 XM_001133896, 
               
               
                   
                   
                   
                   
                   
                 XP_001720207 
                 XM_001720155 
               
               
                   
                   
                 61 
                 CA2 
                 760 
                 NP_000058 
                 NM_000067 
                 Hs.155097 
                 209301_at 
                 73 
               
               
                   
                   
                 62 
                 CCDC3 
                 83643 
                 NP_113643 
                 NM_031455 
                 Hs.498720 
                 223316_at 
                 74 
               
               
                   
                   
                 63 
                 CDS1 
                 1040 
                 NP_001254 
                 NM_001263 
                 Hs.654899 
                 205709_s_at 
                 75 
               
               
                   
                   
                 64 
                 CHN1 
                 1123 
                 NP_001020372, 
                 NM_001025201, 
                 Hs.654534 
                 212624_s_at 
                 76 
               
               
                   
                   
                   
                   
                   
                 NP_001813 
                 NM_001822 
               
               
                   
                   
                 65 
                 CLIC5, 
                 53405, 
                 NP_001107558, 
                 NM_001114086, 
                 Hs.485489 
                 213317_at 
                 77 
               
               
                   
                   
                   
                 LOC100131610 
                 100131610 
                 NP_058625, 
                 NM_016929, 
                   
                 217628_at 
                 78 
               
               
                   
                   
                   
                   
                   
                 XP_001723610 
                 XM_001723558 
                   
                 243917_at 
                 79 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 219866_at 
                 80 
               
               
                   
                   
                 66 
                 CTSH 
                 1512 
                 NP_004381, 
                 NM_004390, 
                 Hs.148641 
                 202295_s_at 
                 81 
               
               
                   
                   
                   
                   
                   
                 NP_683880 
                 NM_148979 
               
               
                   
                   
                 67 
                 CYP7B1 
                 9420 
                 NP_004811 
                 NM_004820 
                 Hs.667720 
                 207386_at 
                 82 
               
               
                   
                   
                 68 
                 DAPK2 
                 23604 
                 NP_055141 
                 NM_014326 
                 Hs.237886 
                 206324_s_at 
                 83 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 215184_at 
                 84 
               
               
                   
                   
                 69 
                 DMRT1 
                 1761 
                 NP_068770 
                 NM_021951 
                 Hs.98586 
                 220493_at 
                 85 
               
               
                   
                   
                 70 
                 DSE 
                 29940 
                 NP_001074445, 
                 NM_001080976, 
                 Hs.486292 
                 218854_at 
                 86 
               
               
                   
                   
                   
                   
                   
                 NP_037484 
                 NM_013352 
               
               
                   
                   
                 71 
                 FBXL17 
                 64839 
                 NP_073735 
                 NM_022824 
                 Hs.657225 
                 227203_at 
                 87 
               
               
                   
                   
                 72 
                 FBXL21 
                 26223 
                 NP_036291 
                 NM_012159 
                 Hs.591275 
                 1555412_at 
                 88 
               
               
                   
                   
                 73 
                 FHOD3 
                 80206 
                 NP_079411 
                 NM_025135 
                 Hs.436636 
                 218980_at 
                 89 
               
               
                   
                   
                 74 
                 H2AFY2 
                 55506 
                 NP_061119 
                 NM_018649 
                 Hs.499953 
                 218445_at 
                 90 
               
               
                   
                   
                 75 
                 HLX 
                 3142 
                 NP_068777 
                 NM_021958 
                 Hs.74870 
                 214438_at 
                 91 
               
               
                   
                   
                 76 
                 IRAK3 
                 11213 
                 NP_001135995, 
                 NM_001142523, 
                 Hs.369265 
                 213817_at 
                 92 
               
               
                   
                   
                   
                   
                   
                 NP_009130 
                 NM_007199 
                   
                 220034_at 
                 93 
               
               
                   
                   
                 77 
                 MACC1 
                 346389 
                 NP_877439 
                 NM_182762 
                 Hs.598388 
                 1566766_a_at 
                 94 
               
               
                   
                   
                 78 
                 MAML3 
                 55534 
                 NP_061187 
                 NM_018717 
                 Hs.586165 
                 242794_at 
                 95 
               
               
                   
                   
                 79 
                 MYO10 
                 4651 
                 NP_036466 
                 NM_012334 
                 Hs.481720 
                 201976_s_at 
                 96 
               
               
                   
                   
                 80 
                 OTUB2 
                 78990 
                 NP_075601 
                 NM_023112 
                 Hs.278815 
                 219369_s_at 
                 97 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 222878_s_at 
                 98 
               
               
                   
                   
                 81 
                 PAPSS2 
                 9060 
                 NP_001015880, 
                 NM_001015880, 
                 Hs.524491 
                 203058_s_at 
                 99 
               
               
                   
                   
                   
                   
                   
                 NP_004661 
                 NM_004670 
                   
                 203060_s_at 
                 100 
               
               
                   
                   
                 82 
                 PCBP3 
                 54039 
                 NP_001123613, 
                 NM_001130141, 
                 Hs.474049 
                 230486_at 
                 101 
               
               
                   
                   
                   
                   
                   
                 NP_065389 
                 NM_020528 
               
               
                   
                   
                 83 
                 PDE4DIP 
                 9659 
                 NP_001002810, 
                 NM_001002810, 
                 Hs.654651 
                 205872_x_at 
                 102 
               
               
                   
                   
                   
                   
                   
                 NP_001002811, 
                 NM_001002811, 
                 Hs.613082 
                 209700_x_at 
                 103 
               
               
                   
                   
                   
                   
                   
                 NP_001002812, 
                 NM_001002812, 
               
               
                   
                   
                   
                   
                   
                 NP_055459, 
                 NM_014644, 
               
               
                   
                   
                   
                   
                   
                 NP_071754 
                 NM_022359 
               
               
                   
                   
                 84 
                 PLD1 
                 5337 
                 NP_001123553, 
                 NM_001130081, 
                 Hs.382865 
                 177_at 
                 104 
               
               
                   
                   
                   
                   
                   
                 NP_002653 
                 NM_002662 
                   
                 215723_s_at 
                 105 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 226636_at 
                 106 
               
               
                   
                   
                 85 
                 PPARG 
                 5468 
                 NP_005028, 
                 NM_005037, 
                 Hs.162646 
                 208510_s_at 
                 107 
               
               
                   
                   
                   
                   
                   
                 NP_056953, 
                 NM_015869, 
               
               
                   
                   
                   
                   
                   
                 NP_619725, 
                 NM_138711, 
               
               
                   
                   
                   
                   
                   
                 NP_619726 
                 NM_138712 
               
               
                   
                   
                 86 
                 PTPN13 
                 5783 
                 NP_006255, 
                 NM_006264, 
                 Hs.436142 
                 243792_x_at 
                 108 
               
               
                   
                   
                   
                   
                   
                 NP_542414, 
                 NM_080683, 
               
               
                   
                   
                   
                   
                   
                 NP_542415, 
                 NM_080684, 
               
               
                   
                   
                   
                   
                   
                 NP_542416 
                 NM_080685 
               
               
                   
                   
                 87 
                 RGS18 
                 64407 
                 NP_570138 
                 NM_130782 
                 Hs.440890 
                 223809_at 
                 109 
               
               
                   
                   
                 88 
                 SIM1 
                 6492 
                 NP_005059 
                 NM_005068 
                 Hs.520293 
                 1556300_s_at 
                 110 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 206876_at 
                 111 
               
               
                   
                   
                 89 
                 SNAI2 
                 6591 
                 NP_003059 
                 NM_003068 
                 Hs.360174 
                 213139_at 
                 112 
               
               
                   
                   
                 90 
                 SOX2 
                 6657 
                 NP_003097 
                 NM_003106 
                 Hs.518438 
                 228038_at 
                 113 
               
               
                   
                   
                 91 
                 SPIRE1 
                 56907 
                 NP_001122098, 
                 NM_001128626, 
                 Hs.515283 
                 1554807_a_at 
                 114 
               
               
                   
                   
                   
                   
                   
                 NP_001122099, 
                 NM_001128627, 
                   
                 224995_at 
                 115 
               
               
                   
                   
                   
                   
                   
                 NP_064533 
                 NM_020148 
                   
                 225018_at 
                 116 
               
               
                   
                   
                 92 
                 TBC1D12 
                 23232 
                 NP_056003 
                 NM_015188 
                 Hs.500598 
                 221858_at 
                 117 
               
               
                   
                   
                 93 
                 TGM5 
                 9333 
                 NP_004236, 
                 NM_004245, 
                 Hs.129719 
                 207911_s_at 
                 118 
               
               
                   
                   
                   
                   
                   
                 NP_963925 
                 NM_201631 
               
               
                   
                   
                 94 
                 TMOD1 
                 7111 
                 NP_003266 
                 NM_003275 
                 Hs.494595 
                 203661_s_at 
                 119 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 203662_s_at 
                 120 
               
               
                   
                   
                 95 
                 TUBB6 
                 84617 
                 NP_115914 
                 NM_032525 
                 Hs.193491 
                 209191_at 
                 121 
               
               
                   
                 Without 
                 96 
                 DDIT4L 
                 115265 
                 NP_660287 
                 NM_145244 
                 Hs.480378 
                 228057_at 
                 122 
               
               
                   
                 stimulation 
                 97 
                 DHRS9 
                 10170 
                 NP_001135742, 
                 NM_001142270, 
                 Hs.179608 
                 219799_s_at 
                 123 
               
               
                   
                   
                   
                   
                   
                 NP_001135743, 
                 NM_001142271, 
                   
                 223952_x_at 
                 124 
               
               
                   
                   
                   
                   
                   
                 NP_005762, 
                 NM_005771, 
                   
                 224009_x_at 
                 125 
               
               
                   
                   
                   
                   
                   
                 NP_954674 
                 NM_199204 
               
               
                   
                   
                 98 
                 ERC2 
                 26059 
                 NP_056391 
                 NM_015576 
                 Hs.476389 
                 213938_at 
                 126 
               
               
                   
                   
                 99 
                 FERMT2 
                 10979 
                 NP_001128471, 
                 NM_001134999, 
                 Hs.509343 
                 209210_s_at 
                 127 
               
               
                   
                   
                   
                   
                   
                 NP_001128472, 
                 NM_001135000, 
               
               
                   
                   
                   
                   
                   
                 NP_006823 
                 NM_006832 
               
               
                   
                   
                 100 
                 HHEX 
                 3087 
                 NP_002720 
                 NM_002729 
                 Hs.118651 
                 204689_at 
                 128 
               
               
                   
                   
                 101 
                 HS3ST1 
                 9957 
                 NP_005105 
                 NM_005114 
                 Hs.507348 
                 205466_s_at 
                 129 
               
               
                   
                   
                 102 
                 NR5A2 
                 2494 
                 NP_003813, 
                 NM_003822, 
                 Hs.33446 
                 208343_s_at 
                 130 
               
               
                   
                   
                   
                   
                   
                 NP_995582 
                 NM_205860 
               
               
                   
                   
                 103 
                 PHLDA1 
                 22822 
                 NP_031376 
                 NM_007350 
                 Hs.602085 
                 217999_s_at 
                 131 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 225842_at 
                 132 
               
               
                   
                   
                 104 
                 RBM20 
                 282996 
                 NP_001127835, 
                 NM_001134363, 
                 Hs.715766 
                 238763_at 
                 133 
               
               
                   
                   
                   
                   
                   
                 XP_001716171, 
                 XM_001716119, 
               
               
                   
                   
                   
                   
                   
                 XP_291671, 
                 XM_291671, 
               
               
                   
                   
                   
                   
                   
                 XP_944430 
                 XM_939337 
               
               
                   
                   
                 105 
                 NINL 
                 22981 
                 NP_079452 
                 NM_025176 
                 Hs.696157 
                 207705_s_at 
                 134 
               
               
                   
                   
                 106 
                 RTN2 
                 6253 
                 NP_005610, 
                 NM_005619, 
                 Hs.47517 
                 34408_at 
                 135 
               
               
                   
                   
                   
                   
                   
                 NP_996783, 
                 NM_206900, 
               
               
                   
                   
                   
                   
                   
                 NP_996784 
                 NM_206901 
               
               
                   
                   
                 107 
                 SH3RF2 
                 153769 
                 NP_689763 
                 NM_152550 
                 Hs.443728 
                 243582_at 
                 136 
               
               
                   
                   
                 108 
                 TSHZ2 
                 128553 
                 NP_775756 
                 NM_173485 
                 Hs.649877 
                 220213_at 
                 137 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Hs.271605 
                 243940_at 
                 138 
               
               
                   
                 With 
                 109 
                 EML1 
                 2009 
                 NP_001008707, 
                 NM_001008707, 
                 Hs.12451 
                 204796_at 
                 139 
               
               
                   
                 stimulation 
                   
                   
                   
                 NP_004425 
                 NM_004434 
                   
                 204797_s_at 
                 140 
               
               
                   
                   
                 110 
                 HIST1H2BC 
                 8347 
                 NP_003517 
                 NM_003526 
                 Hs.658713 
                 236193_at 
                 141 
               
               
                   
                   
                 111 
                 MAP3K4 
                 4216 
                 NP_005913, 
                 NM_005922, 
                 Hs.390428 
                 204089_x_at 
                 142 
               
               
                   
                   
                   
                   
                   
                 NP_006715 
                 NM_006724 
                   
                 216199_s_at 
                 143 
               
               
                   
                   
                 112 
                 PDK4 
                 5166 
                 NP_002603 
                 NM_002612 
                 Hs.8364 
                 225207_at 
                 144 
               
               
                   
                   
                 113 
                 RGS2 
                 5997 
                 NP_002914 
                 NM_002923 
                 Hs.78944 
                 202388_at 
                 145 
               
               
                   
                   
                 114 
                 RGS20 
                 8601 
                 NP_003693, 
                 NM_003702, 
                 Hs.368733 
                 210138_at 
                 146 
               
               
                   
                   
                   
                   
                   
                 NP_733466 
                 NM_170587 
               
               
                 Unknown 
                 Common 
                 115 
                 — 
                 — 
                 — 
                 AK055628, 
                 Hs.594351 
                 226777_at 
                 147 
               
               
                   
                   
                   
                   
                   
                   
                 uc001ljj.1 
               
               
                   
                   
                 116 
                 — 
                 — 
                 — 
                 AA416573, 
                 Hs.654918 
                 229951_x_at 
                 148 
               
               
                   
                   
                   
                   
                   
                   
                 AA628762, 
               
               
                   
                   
                   
                   
                   
                   
                 D53835, 
               
               
                   
                   
                   
                   
                   
                   
                 D53836, 
               
               
                   
                   
                   
                   
                   
                   
                 H24473, 
               
               
                   
                   
                   
                   
                   
                   
                 R37871, 
               
               
                   
                   
                   
                   
                   
                   
                 R40232, 
               
               
                   
                   
                   
                   
                   
                   
                 T10348, 
               
               
                   
                   
                   
                   
                   
                   
                 T23451, 
               
               
                   
                   
                   
                   
                   
                   
                 W56351, 
               
               
                   
                   
                   
                   
                   
                   
                 W57867, 
               
               
                   
                   
                   
                   
                   
                   
                 Z28733 
               
               
                   
                   
                 117 
                 — 
                 — 
                 — 
                 AA687415, 
                 Hs.434948 
                 238009_at 
                 149 
               
               
                   
                   
                   
                   
                   
                   
                 AA96901, 
               
               
                   
                   
                   
                   
                   
                   
                 AI291640, 
               
               
                   
                   
                   
                   
                   
                   
                 AI446064, 
               
               
                   
                   
                   
                   
                   
                   
                 AI634557, 
               
               
                   
                   
                   
                   
                   
                   
                 AI694948, 
               
               
                   
                   
                   
                   
                   
                   
                 AI701854, 
               
               
                   
                   
                   
                   
                   
                   
                 AI983938, 
               
               
                   
                   
                   
                   
                   
                   
                 AV745212, 
               
               
                   
                   
                   
                   
                   
                   
                 AV745909, 
               
               
                   
                   
                   
                   
                   
                   
                 AV746001, 
               
               
                   
                   
                   
                   
                   
                   
                 AW008696, 
               
               
                   
                   
                   
                   
                   
                   
                 AW511701, 
               
               
                   
                   
                   
                   
                   
                   
                 AW974416, 
               
               
                   
                   
                   
                   
                   
                   
                 BG149302, 
               
               
                   
                   
                   
                   
                   
                   
                 BG150103, 
               
               
                   
                   
                   
                   
                   
                   
                 N66771, 
               
               
                   
                   
                   
                   
                   
                   
                 R66991 
               
               
                   
                   
                 118 
                 — 
                 — 
                 — 
                 AI148241, 
                 Hs.659083 
                 238151_at 
                 150 
               
               
                   
                   
                   
                   
                   
                   
                 AI735444, 
               
               
                   
                   
                   
                   
                   
                   
                 BE645654, 
               
               
                   
                   
                   
                   
                   
                   
                 BF510855, 
               
               
                   
                   
                   
                   
                   
                   
                 BF511636 
               
               
                   
                   
                 119 
                 — 
                 — 
                 — 
                 AK094629 
                 Hs.594896 
                 238623_at 
                 151 
               
               
                   
                 Without 
                 120 
                 C1orf106 
                 55765 
                 NP_001136041, 
                 NM_001142569, 
                 Hs.518997 
                 219010_at 
                 152 
               
               
                   
                 stimulation 
                   
                   
                   
                 NP_060735 
                 NM_018265 
               
               
                   
                   
                 121 
                 C6orf145 
                 221749 
                 NP_899229 
                 NM_183373 
                 Hs.484500 
                 212923_s_at 
                 153 
               
               
                   
                   
                 122 
                 LOC401097 
                 401097 
                 XP_001717155, 
                 XM_001717103, 
                 Hs.710781 
                 236738_at 
                 154 
               
               
                   
                   
                   
                   
                   
                 XP_001718614, 
                 XM_001718562, 
               
               
                   
                   
                   
                   
                   
                 XP_001718795 
                 XM_001718743 
               
               
                   
                   
                 123 
                 MAMLD1 
                 10046 
                 NP_005482 
                 NM_005491 
                 Hs.20136 
                 205088_at 
                 155 
               
               
                   
                   
                 124 
                 ZC3H12C 
                 85463 
                 NP_203748 
                 NM_033390 
                 Hs.376289 
                 231899_at 
                 156 
               
               
                   
                   
                 125 
                 — 
                 — 
                 — 
                 AA579799, 
                 Hs.663788 
                 215768_at 
                 157 
               
               
                   
                   
                   
                   
                   
                   
                 AA947186, 
               
               
                   
                   
                   
                   
                   
                   
                 AL049337, 
               
               
                   
                   
                   
                   
                   
                   
                 AW665328 
               
               
                   
                   
                 126 
                 — 
                 — 
                 — 
                 AK093229 
                 Hs.586723 
                 222900_at 
                 158 
               
               
                   
                   
                 127 
                 — 
                 — 
                 — 
                 AK129763, 
                 Hs.157726 
                 227452_at 
                 159 
               
               
                   
                   
                   
                   
                   
                   
                 CR595588, 
               
               
                   
                   
                   
                   
                   
                   
                 uc002jiy.1, 
               
               
                   
                   
                   
                   
                   
                   
                 uc002jiz.1 
               
               
                   
                   
                 128 
                 — 
                 — 
                 — 
                 AI766299 
                 — 
                 236338_at 
                 160 
               
               
                   
                   
                 129 
                 — 
                 — 
                 — 
                 AI262017, 
                 Hs.666775 
                 237923_at 
                 161 
               
               
                   
                   
                   
                   
                   
                   
                 AI280978, 
               
               
                   
                   
                   
                   
                   
                   
                 AI284950, 
               
               
                   
                   
                   
                   
                   
                   
                 AI733224, 
               
               
                   
                   
                   
                   
                   
                   
                 AI733801 
               
               
                   
                   
                 130 
                 — 
                 — 
                 — 
                 AI682088, 
                 Hs.606172 
                 241726_at 
                 162 
               
               
                   
                   
                   
                   
                   
                   
                 AI951058, 
               
               
                   
                   
                   
                   
                   
                   
                 F06296, 
               
               
                   
                   
                   
                   
                   
                   
                 F13164, 
               
               
                   
                   
                   
                   
                   
                   
                 T77624, 
               
               
                   
                   
                   
                   
                   
                   
                 Z44722 
               
               
                   
                 With 
                 131 
                 C12orf64 
                 283310 
                 NP_775862 
                 NM_173591 
                 Hs.355145 
                 1553746_a_at 
                 163 
               
               
                   
                 stimulation 
                 132 
                 C6orf168 
                 84553 
                 NP_115900 
                 NM_032511 
                 Hs.573245 
                 232067_at 
                 164 
               
               
                   
                   
                 133 
                 CAMSAP1L1 
                 23271 
                 NP_982284 
                 NM_203459 
                 Hs.23585 
                 217196_s_at 
                 165 
               
               
                   
                   
                 134 
                 MAGED4, 
                 728239, 
                 NP_001092270, 
                 NM_001098800, 
                 Hs.571729 
                 223313_s_at 
                 166 
               
               
                   
                   
                   
                 MAGED4B 
                 81557 
                 NP_110428, 
                 NM_030801, 
               
               
                   
                   
                   
                   
                   
                 NP_803879, 
                 NM_177535, 
               
               
                   
                   
                   
                   
                   
                 NP_803881 
                 NM_177537 
               
               
                   
                   
                 135 
                 — 
                 — 
                 — 
                 AK093612 
                 Hs.663643 
                 1556602_at 
                 167 
               
               
                   
                   
                 136 
                 — 
                 — 
                 — 
                 BC010059 
                 Hs.637648 
                 1562957_at 
                 168 
               
               
                   
                   
                 137 
                 — 
                 — 
                 — 
                 GENSCAN00000030683 
                 — 
                 227985_at 
                 169 
               
               
                   
                   
                 138 
                 — 
                 — 
                 — 
                 AK027107 
                 Hs.655798 
                 232331_at 
                 170 
               
               
                   
                   
                 139 
                 — 
                 — 
                 — 
                 AI269134, 
                 Hs.657330 
                 235438_at 
                 171 
               
               
                   
                   
                   
                   
                   
                   
                 AI312873, 
               
               
                   
                   
                   
                   
                   
                   
                 AI671475, 
               
               
                   
                   
                   
                   
                   
                   
                 AV656012, 
               
               
                   
                   
                   
                   
                   
                   
                 AW162011, 
               
               
                   
                   
                   
                   
                   
                   
                 BG151392, 
               
               
                   
                   
                   
                   
                   
                   
                 H69527, 
               
               
                   
                   
                   
                   
                   
                   
                 N43169, 
               
               
                   
                   
                   
                   
                   
                   
                 Z36958 
               
               
                   
                   
                 140 
                 — 
                 — 
                 — 
                 AI435469, 
                 Hs.656932 
                 241022_at 
                 172 
               
               
                   
                   
                   
                   
                   
                   
                 BF111679, 
               
               
                   
                   
                   
                   
                   
                   
                 BF112253, 
               
               
                   
                   
                   
                   
                   
                   
                 R37814 
               
               
                   
                   
                 141 
                 — 
                 — 
                 — 
                 AA846423, 
                 Hs.665895 
                 243922_at 
                 173 
               
               
                   
                   
                   
                   
                   
                   
                 AI022103, 
               
               
                   
                   
                   
                   
                   
                   
                 BF061333 
               
               
                   
                   
                 142 
                 — 
                 — 
                 — 
                 AA648972, 
                 Hs.602350 
                 244247_at 
                 174 
               
               
                   
                   
                   
                   
                   
                   
                 AA879467, 
               
               
                   
                   
                   
                   
                   
                   
                 AI802768, 
               
               
                   
                   
                   
                   
                   
                   
                 AW974600 
               
               
                   
               
            
           
         
       
     
     It is believed that detection of the polynucleotide markers shown in Table 9 by well-known methods in the art such as PCR or detection of proteins encoded by these polynucleotide markers by well-known methods in the art such as ELISA or flow cytometry allows specific detection of human Th17 cells. 
     EXAMPLE 2 
     Expression Analysis of Protein Markers for Detecting Human Th17 Cells 
     1. Preparation of Measurement Samples 
     (1) Preparation of MCAM Measurement Samples 
     To Th17 cells “without activation stimulation” (5×10 6  cells/ml) prepared in Example 1 under the paragraph “2. Cell culture” was added a phycoerythrin (PE)-labeled anti-MCAM antibody (BioLegend) to a final concentration of 1.25 μg/ml and reaction was carried out at 4° C. for 20 minutes. 
     After the reaction, Th17 cells were washed by adding phosphate buffered saline (PBS) containing 0.5% BSA and centrifuging to collect the cells. The washed Th17 cells were suspended in PBS containing 0.5 μg/ml 7-amino-actinomycin D (7-AAD) and 0.5% BSA to prepare a MCAM measurement sample of Th17 cells (5×10 6  cells/ml). 
     MCAM measurement samples of Th1 cells (5×10 6  cells/ml), of Th2 cells (5×10 6  cells/ml) and of Treg cells (5×10 6  cells/ml) were prepared in the similar manner as above except that Th1, Th2 and Treg cells “without activation stimulation”, respectively, were used instead of Th17 cells “without activation stimulation”. 
     A negative control sample (5×10 6  cells/ml) was prepared by adding a PE-labeled mouse IgG2a isotype control (BioLegend) to a final concentration of 1.0 μg/ml instead of the PE-labeled MCAM antibody and reacting at 4° C. for 20 minutes. 
     (2) Preparation of PTPRM Measurement Samples 
     To Th17 cells “without activation stimulation” (5×10 6  cells/ml) prepared in Example 1 under the paragraph “2. Cell culture” was added an anti-PTPRM antibody (Abcam) to a final concentration of 2.0 μg/ml and reaction was carried out at 4° C. for 20 minutes. 
     After the reaction, Th17 cells were added with PBS containing 0.5% BSA and centrifuged to collect the cells. The collected Th17 cells were suspended in PBS containing 0.5% BSA. The suspension was added with a PE-labeled anti-mouse IgG antibody (BioLegend) to a final concentration of 1.0 μg/ml and reaction was carried out at 4° C. for 20 minutes. 
     After reaction with the PE-labeled anti-mouse IgG antibody, Th17 cells were washed by adding PBS containing 0.5% BSA and centrifuging to collect the cells. The washed Th17 cells were suspended in PBS containing 0.5 μg/ml 7-amino-actinomycin D (7-AAD) and 0.5% BSA to prepare a PTPRM measurement sample of Th17 cells (5×10 6  cells/ml). 
     PTPRM measurement samples of Th1 cells (5×10 6  cells/ml), of Th2 cells (5×10 6  cells/ml) and of Treg cells (5×10 6  cells/ml) were prepared in the similar manner as above except that Th1, Th2 and Treg cells “without activation stimulation”, respectively, were used instead of Th17 cells “without activation stimulation”. 
     A negative control sample (5×10 6  cells/ml) was prepared by adding a mouse IgG2a isotype control (BioLegend) to a final concentration of 1.0 μg/ml instead of the anti-PTPRM antibody and reacting at 4° C. for 20 minutes. 
     (3) Preparation of CCR6 Measurement Samples 
     CCR6 measurement samples of Th17 cells (5×10 6  cells/ml), of Th1 cells (5×10 6  cells/ml), of Th2 cells (5×10 6  cells/ml) and of Treg cells (5×10 6  cells/ml) were prepared in the similar manner as the above paragraph “(1) Preparation of MCAM measurement samples” except that a PE-labeled anti-CCR6 antibody (BD Bioscience) was used at a final concentration of 1.0 μg/ml instead of the PE-labeled anti-MCAM antibody. 
     A negative control sample (5×10 6  cells/ml) was prepared by adding a PE-labeled mouse IgG1 isotype control (BioLegend) to a final concentration of 1.0 μg/ml instead of the PE-labeled anti-CCR6 antibody and reacting at 4° C. for 20 minutes. 
     (4) Preparation of FOXP3 Measurement Samples 
     Th17 cells “without activation stimulation” (5×10 6  cells/ml) prepared in Example 1 under the paragraph “2. Cell culture” were fixed and permeability of the cell membranes was increased using FOXP3 staining buffer set (eBioscience) before addition of a PE-labeled anti-FOXP3 antibody (BioLegend) to a final concentration of 3.125 μg/ml and reaction at 4° C. for 20 minutes. 
     After the reaction, Th17 cells were washed by adding phosphate buffered saline (PBS) containing 0.5% BSA and centrifuging to collect the cells. The washed Th17 cells were suspended in PBS containing 0.5% BSA to prepare a FOXP3 measurement sample of Th17 cells (5×10 6  cells/ml). 
     FOXP3 measurement samples of Th1 cells (5×10 6  cells/ml), of Th2 cells (5×10 6  cells/ml) and of Treg cells (5×10 6  cells/ml) were prepared in the similar manner as above except that Th1, Th2 and Treg cells “without activation stimulation”, respectively, were used instead of Th17 cells “without activation stimulation”. 
     A negative control sample (5×10 6  cells/ml) was prepared by adding a PE-labeled mouse IgG1 isotype control (BioLegend) to a final concentration of 1.0 μg/ml instead of the PE-labeled FOXP3 antibody and reacting at 4° C. for 20 minutes. 
     (5) Preparation of GRP34 Measurement Samples 
     Th17 cells “without activation stimulation” prepared in Example 1 under the paragraph “2. Cell culture” were prepared in 5% FBS/RPMI at 2.5×10 5  cells/ml. Phorbol myristate acetate at a final concentration of 50 ng/ml and ionomycin at a final concentration of 1 μM were added and incubated at 37° C. for 4 hours to stimulate Th17 cells. Then, brefeldin A was added to a final concentration of 10 μg/ml and incubated at 37° C. for 2 hours. 
     After cultivation, Th17 cells were washed twice by adding phosphate buffered saline (PBS) containing 0.5% BSA and centrifuging to collect the cells. The washed Th17 cells were added with 2% paraformaldehyde to fix the cells. After fixing the cells, a saponin buffer (0.5% saponin, 0.5% bovine serum albumin (BSA), 1 mM sodium azide (in PBS)) was added to accelerate cell membrane permeability of Th17 cells. 
     The sample after saponin treatment was added with an anti-GPR34 antibody (Lifespan Biosciences) to a final concentration of 25.0 μg/ml and reaction was carried out at 4° C. for 20 minutes. After the reaction, the saponin buffer was added and Th17 cells were collected by centrifugation. The collected Th17 cells were suspended in the saponin buffer. The suspension was added with a PE-labeled anti-mouse IgG antibody (BioLegend) to a final concentration of 1.0 μg/ml and reaction was carried out at 4° C. for 20 minutes. 
     After the reaction with the PE-labeled anti-mouse IgG antibody, Th17 cells were washed twice by adding the saponin buffer and centrifuging to collect the cells. The washed Th17 cells were suspended in PBS containing 0.5% BSA to prepare a GRP34 measurement sample of Th17 cells (2.5×10 5  cells/ml). 
     GRP34 measurement samples of Th1 cells, of Th2 cells and of Treg cells were prepared in the similar manner as above except that Th1, Th2 and Treg cells “without activation stimulation”, respectively, were used instead of Th17 cells “without activation stimulation”. 
     A negative control sample (2.5×10 6  cells/ml) was prepared by adding a mouse IgG2a isotype control (BioLegend) to a final concentration of 1.0 μg/ml instead of the anti-GPR34 antibody and reacting at 4° C. for 20 minutes. 
     (6) Preparation of IL-17a Measurement Samples 
     Th17 cells “without activation stimulation” prepared in Example 1 under the paragraph “2. Cell culture” were prepared in 5% FBS/RPMI at 2.5×10 5  cells/ml. Phorbol myristate acetate at a final concentration of 50 ng/ml and ionomycin at a final concentration of 1 μM were added and incubated at 37° C. for 4 hours to stimulate Th17 cells. Then, brefeldin A was added to a final concentration of 10 μg/ml and incubated at 37° C. for 2 hours. 
     After cultivation, Th17 cells were washed by adding phosphate buffered saline (PBS) containing 0.5% BSA and centrifuging to collect the cells. The washed Th17 cells were added with 2% paraformaldehyde to fix the cells. After fixing the cells, a saponin buffer (0.5% saponin, 0.5% bovine serum albumin (BSA), 1 mM sodium azide (in PBS)) was added to accelerate cell membrane permeability of Th17 cells. 
     The sample after saponin treatment was added with a PerCP-Cy5.5-labeled anti-IL-17A antibody (eBioscience) to a final concentration of 0.15 μg/ml and reaction was carried out at 4° C. for 20 minutes. 
     After the reaction, Th17 cells were washed by adding the saponin buffer and centrifuging to collect cells. The washed Th17 cells were suspended in PBS containing 0.5% BSA to prepare a IL-17A measurement sample of Th17 cells (2.5×10 5  cells/ml). 
     A negative control sample (2.5×10 6  cells/ml) was prepared by adding a PerCP-Cy5.5-labeled mouse IgG1 isotype control (eBioscience) to a final concentration of 1.0 μg/ml instead of the PerCP-Cy5.5-labeled anti-IL-17A antibody. 
     (7) Preparation of IFN-γ Measurement Samples 
     IFN-γ measurement samples of Th17 cells (2.5×10 5  cells/ml), of Th1 cells (2.5×10 5  cells/ml), of Th2 cells (2.5×10 5  cells/ml) and of Treg cells (2.5×10 5  cells/ml) were prepared in the similar manner as the above paragraph “(6) Preparation of IL-17A measurement samples” except that an Alexa488-labeled anti-IFN-γ antibody (BioLegend) was used at a final concentration of 1.0 μg/ml instead of the PerCP-Cy5.5-labeled anti-IL-17A antibody. 
     A negative control sample (2.5×10 6  cells/ml) was prepared by adding an Alex488-labeled mouse IgG 1 isotype control (BioLegend) to a final concentration of 1.0 μg/ml instead of the Alexa488-labeled anti-IFN-γ antibody and reacting at 4° C. for 20 minutes. 
     (8) Preparation of IL-4 Measurement Samples 
     IL-4 measurement samples of Th17 cells (2.5×10 5  cells/ml), of Th1 cells (2.5×10 5  cells/ml), of Th2 cells (2.5×10 5  cells/ml) and of Treg cells (2.5×10 5  cells/ml) were prepared in the similar manner as the above paragraph “(6) Preparation of IL-17A measurement samples” except that an APC-labeled anti-IL-4 antibody (eBioscience) was used at a final concentration of 0.2 μg/ml instead of the PerCP-Cy5.5-labeled anti-IL-17A antibody. 
     A negative control sample (2.5×10 6  cells/ml) was prepared by adding an APC-labeled rat IgG1 isotype control (BioLegend) to a final concentration of 1.0 μg/ml instead of the APC-labeled anti-IL-4 antibody and reacting at 4° C. for 20 minutes. 
     2. Expression Analysis of Protein Markers in Measurement Samples Using Flow Cytometer 
     The prepared measurement samples were analyzed by FACSCanto II (BD Bioscienct) and FACS DIVA software (BD Bioscience). Histograms (particle size distribution) of fluorescent intensities obtained by the analysis are shown in  FIGS. 2 to 9 , which correspond respectively to the histograms obtained from MCAM measurement samples, PTPRM measurement samples, GPR34 measurement samples, CCR6 measurement samples, IL-17A measurement samples, IFN-γ measurement samples, IL-4 measurement samples, and FOXP3 measurement samples. In  FIGS. 2 to 9 , the vertical axis of the histograms shows the number of cells and the horizontal axis shows the fluorescent intensity. The numbers at the upper right of the histograms correspond to the ratio (%) of positive cells for the marker gene relative to the number of total cells in the respective measurement samples. The cells were determined as positive or negative based on the maximal fluorescent intensity in the negative control. Namely, the cells having higher fluorescent intensity than the maximal fluorescent intensity of the negative control were determined as positive, while the cells having a fluorescent intensity equal to or lower than the maximal fluorescent intensity of the negative control were determined as negative. The ratio of positive cells was calculated as the ratio of the number of positive cells relative to the number of total cells. 
     CCR6 and IL-17A are known markers for Th17 cells.  FIGS. 5 and 6  show that the expression levels of CCR6 and IL-17A proteins are high in Th17 cells. IFN-γ is a known marker for Th1 cells.  FIG. 7  shows that the expression level of IFN-γ protein is high in Th1 cells. IL-4 is a known marker for Th2 cells.  FIG. 8  shows that the expression level of IL-4 protein is high in Th2 cells. FOXP3 is a known marker for Treg cells.  FIG. 9  shows that the expression level of FOXP3 protein is high in Treg cells. Thus, it is indicated that these measurement samples are suitable for expression analysis of protein markers. 
       FIGS. 2 to 4  show that the expression levels of MCAM, PTPRM and GPR34 proteins are high in Th17 cells. It is also found that the ratios of positive cells in the MCAM measurement sample, PTPRM measurement sample and GPR34 measurement sample of Th17 cells were equal to or higher than the ratios of positive cells in the CCR6 measurement sample and IL-17A measurement sample. This reveals that the proteins encoded by the genes MCAM, PTPRM and GPR34 which were identified in Example 1 as the polynucleotide markers for detecting Th17 cells can also be used as protein markers for detecting Th17 cells. 
     EXAMPLE 3 
     Expression Analysis of Polynucleotide Markers for Detecting Th17 Cells by Real-Time PCR 
     1. Preparation of cDNA 
     (1) Preparation of cDNA from Cells “without Activation Stimulation” 
     Total RNA (0.1 μg) of Th17 cells “without activation stimulation” extracted in Example 1 under the paragraph “3. Extraction of total RNA” was reverse-transcribed with a poly dT primer (Hokkaido System Science Co., Ltd.), random primers (Hokkaido System Science Co., Ltd.) and Superscript III reverse transcriptase (Invitrogen Corporation) to obtain cDNA of Th17 cells “without activation stimulation”. Reverse transcription was carried out according to the attached instructions. 
     cDNAs of Th1 cells “without activation stimulation”, of Th2 cells “without activation stimulation” and of Treg cells “without activation stimulation” were prepared in the similar manner as above except that total RNAs (0.1 μg) of Th1 cells, Th2 cells and Treg cells “without activation stimulation” were used instead of total RNA (0.1 μg) of Th17 cells “without stimulation”. 
     The number of samples of the cells “without activation stimulation” used for preparation of cDNA is shown in Table 10. 
                                     TABLE 10                   Th1                       cells   Th2 cells   Th17 cells   Treg cells                                                    w/o activation stimulation   5   5   5   4                    
(2) Preparation of cDNA from Cells “with Activation Stimulation”
 
     Th17 cells “without activation stimulation” prepared in Example 1 under the paragraph “2. Cell culture” were prepared in 5% FBS/RPMI at 2.5×10 5  cells/ml. Th17 cells were stimulated by incubating the cells at 37° C. for 3 hours with T cell activation/expansion kit (Miltenyi Biotec). These Th17 cells “with activation stimulation” were subjected to extraction of total RNA in the same manner as Example 1, “3. Extraction of total RNA”. The extracted total RNA (0.1 μg) of Th17 cells “with activation stimulation” was reverse-transcribed with a poly dT primer (Hokkaido System Science Co., Ltd.), random primers (Hokkaido System Science Co., Ltd.) and Superscript III reverse transcriptase (Invitrogen Corporation) to obtain cDNA of Th17 cells “with activation stimulation”. Reverse transcription was carried out according to the attached instructions. 
     cDNAs of Th1 cells “with activation stimulation”, of Th2 cells “with activation stimulation” and of Treg cells “with activation stimulation” were prepared in the similar manner as above except that total RNAs (0.1 μg) of Th1 cells, Th2 cells and Treg cells “with activation stimulation” were used instead of total RNA (0.1 μg) of Th17 cells “with activation stimulation”. 
     The number of samples of the cells “with activation stimulation” used for preparation of cDNA is shown in Table 11. 
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 11 
               
               
                   
               
               
                   
                 Th1 cells 
                 Th2 cells 
                 Th17 cells 
                 Treg cells 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 w/ activation stimulation 
                 5 
                 5 
                 5 
                 3 
               
               
                   
               
            
           
         
       
     
     2. Design of Primer Sets 
     The following primer sets were designed with Primer3 software. 
     (1) Primer Sets for Detecting Th17 Cells 
     Primer sets were designed for the genes ADAM12, ATP6V0A4, ATP9A, BVES, C5orf40, CDH4, DIO2, L1CAM, MCAM, SHROOM2, TMEM163, UPK1B, DRD2, PGBD5 (LOC100134440), ODZ4, SLC6A15, AKAP12, C9orf125, POPDC3, UNC13C, PCOLCE2, PNOC, TGFBI, IL1A, BHLHE22, PPARG, SIM1 and SNAI2, which were detected in Example 1 as the polynucleotide markers for detecting Th17 cells. 
     (2) Primer Sets for Known Markers for Th17 Cells 
     Primer sets were designed for known gene markers for Th17 cells, CCR6, RORC and IL-17A. 
     (3) Primer Sets for Known Markers for Th1 Cells 
     Primer sets were designed for known gene markers for Th1 cells, TBX21 and IFN-γ. 
     (4) Primer Sets for Known Markers for Th2 Cells 
     Primer sets were designed for known gene markers for Th2 cells, GATA3 and IL-4. 
     (5) Primer Sets for Known Markers for Treg Cells 
     Primer sets were designed for a known gene marker for Treg cells, FOXP3. 
     (6) Primer Sets for Internal Controls 
     Primer sets were designed for internal control genes, Gapdh, ACTB, B2M and UBC. 
     Designed primer sets are shown in Table 12. 
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 12 
               
               
                   
               
               
                   
                   
                 SEQ 
                   
                 SEQ 
               
               
                 Gene 
                   
                 ID 
                   
                 ID 
               
               
                 symbol 
                 Forward primer 
                 NO: 
                 Reverse primer 
                 NO: 
               
               
                   
               
             
            
               
                 ADAM12 
                 TCTCCCTCGCTCGAAATTACA 
                 181 
                 CAGAATATCCCCGTACATGTCCAT 
                 182 
               
               
                   
               
               
                 ATP6V0A4 
                 TCCTTGAACATCTTTGGCTCTTC 
                 183 
                 TCCATGTGCCGTTTCTGAAC 
                 184 
               
               
                   
               
               
                 ATP9A 
                 AGAGGAGCAGTATCAGGACTTTGAA 
                 185 
                 AGCGGTCGTGCACACTCA 
                 186 
               
               
                   
               
               
                 BVES 
                 CGGCTTGCACCAGTTTCTTC 
                 187 
                 GCTCCTTCTTCTATCGGTTTCATC 
                 188 
               
               
                   
               
               
                 C5orf40 
                 TCGGAGGGCAGAGCTCTAAC 
                 189 
                 CCTCGATGTTCATCCCGATT 
                 190 
               
               
                   
               
               
                 CDH4 
                 GATCAGCCCCACTCTCCAAA 
                 191 
                 GATGGATCCCCACTGATGATG 
                 192 
               
               
                   
               
               
                 DIO2 
                 CATGATGCTAAGAGTCCTGGGTAA 
                 193 
                 TTCTGCAACTGAGAAGCACATATG 
                 194 
               
               
                   
               
               
                 L1CAM 
                 CAAGGAGGGCCAGTGCAA 
                 195 
                 GAAGCCCCACCCTTCTCTTC 
                 196 
               
               
                   
               
               
                 MCAM 
                 GGGCATCCCTGTGAACAGTAA 
                 197 
                 GGTACCCGTTCCTCCCTACAC 
                 198 
               
               
                   
               
               
                 SHROOM2 
                 TGCATGTTAATGGTGAGTGAATCC 
                 199 
                 TTGATCCAACAAATGCCCTAATAC 
                 200 
               
               
                   
               
               
                 TMEM163 
                 GGTCAAACTCCTCATCGACATG 
                 201 
                 CCCCTTCACTCAAACATCTCGTA 
                 202 
               
               
                   
               
               
                 UPK1B 
                 CCAGTGGAAAAACAATGGAGTCA 
                 203 
                 ACAGCAATTGTCCTGGAGCAT 
                 204 
               
               
                   
               
               
                 DRD2 
                 CTGCTCATCGCTGTCATCGT 
                 205 
                 CGGGACACAGCCATGCA 
                 206 
               
               
                   
               
               
                 PGBD5 
                 AGAGTTTGAGAAGCAAGGGATTTACT 
                 207 
                 GGCCGGTGCAGTCACTCTT 
                 208 
               
               
                   
               
               
                 ODZ4 
                 GCCCACAGACTTAGCCATCA 
                 209 
                 TCCCGGCGACAATGC 
                 210 
               
               
                   
               
               
                 SLC6A15 
                 TGCCACCACCTATTACTGGTACA 
                 211 
                 AGTTTAAGCCCCCACTTTCAGAA 
                 212 
               
               
                   
               
               
                 AKAP12 
                 TCCATAGCTGGGTCTGGTGTAGA 
                 213 
                 TTCTTGATTGAGACCCAGGATTC 
                 214 
               
               
                   
               
               
                 C9orf125 
                 GAGAGGCTCCAGCACTACATCA 
                 215 
                 CTACACCAACCCATTCCAGGAT 
                 216 
               
               
                   
               
               
                 POPDC3 
                 TTCAGTTCCTGGATTCTCCTGAGT 
                 217 
                 CAGTGAGGGTTACCTGAAAAATGC 
                 218 
               
               
                   
               
               
                 UNC13C 
                 TCAGGGACCAACCACCAAGA 
                 219 
                 CAGGACAGGTGTGTAGGCAGTTT 
                 220 
               
               
                   
               
               
                 PCOLCE2 
                 CCACCACATTCCCTGTAACCA 
                 221 
                 TCCGTCTACACTTTTGTTGACACA 
                 222 
               
               
                   
               
               
                 PNOC 
                 CTCAGTCTCTTCTCCAGTGTGTTCA 
                 223 
                 GGAGCTTCTCCTGGCATGTG 
                 224 
               
               
                   
               
               
                 TGFBI 
                 GGGCGGCAAAAAACTGAGA 
                 225 
                 CCGCGATGCAGGTGTTCT 
                 226 
               
               
                   
               
               
                 IL1A 
                 CAATTGTATGTGACTGCCCAAGA 
                 227 
                 TGGGTATCTCAGGCATCTCCTT 
                 228 
               
               
                   
               
               
                 BHLHE22 
                 TGCTCCCCACCCCCTTTA 
                 229 
                 CTGCTTTGTTTGCTCTGCAAGT 
                 230 
               
               
                   
               
               
                 PPARG 
                 CCTGAGCCACTGCCAACATT 
                 231 
                 AGGTGTCAGATTTTCCCTCAGAAT 
                 232 
               
               
                   
               
               
                 SIM1 
                 CATGCCTCACATCGCTTCAG 
                 233 
                 CCACACTATCTTCATCCCAATGAC 
                 234 
               
               
                   
               
               
                 SNAI2 
                 CTTGCCCTCACTGCAACAGA 
                 235 
                 TCTGCAGATGAGCCCTCAGA 
                 236 
               
               
                   
               
               
                 TBX21 
                 GATGCGCCAGGAAGTTTCA 
                 237 
                 GACGCCCCCTTGTTGTTTG 
                 238 
               
               
                   
               
               
                 GATA3 
                 GCGGGCTCTATCACAAAATGA 
                 239 
                 GCCTTCGCTTGGGCTTAAT 
                 240 
               
               
                   
               
               
                 FOXP3 
                 CACCTGGCTGGGAAAATGG 
                 241 
                 GGAGCCCTTGTCGGATGAT 
                 242 
               
               
                   
               
               
                 CCR6 
                 GGCAGTTCTCCAGGCTATTTGT 
                 243 
                 GGAGGCCAAAGACACAGATCA 
                 244 
               
               
                   
               
               
                 RORC 
                 CCAAGGCTCAGTCATGAGAACA 
                 245 
                 GCGGAAGAAGCCCTTGCA 
                 246 
               
               
                   
               
               
                 IFNG 
                 CCAACGCAAAGCAATACATGA 
                 247 
                 CGAAACAGCATCTGACTCCTTTT 
                 248 
               
               
                   
               
               
                 IL4 
                 TGGGTCTCACCTCCCAACTG 
                 249 
                 GCCGGCACATGCTAGCA 
                 250 
               
               
                   
               
               
                 IL17A 
                 CCCAAAAGGTCCTCAGATTACTACA 
                 251 
                 CATTGCGGTGGAGATTCCA 
                 252 
               
               
                   
               
               
                 GAPDH 
                 ACCCACTCCTCCACCTTTGA 
                 253 
                 TTGCTGTAGCCAAATTCGTTGT 
                 254 
               
               
                   
               
               
                 ACTB 
                 CAGCAGATGTGGATCAGCAAG 
                 255 
                 GCATTTGCGGTGGACGAT 
                 256 
               
               
                   
               
               
                 B2M 
                 TGCTGTCTCCATGTTTGATGTATCT 
                 257 
                 TCTCTGCTCCCCACCTCTAAGT 
                 258 
               
               
                   
               
               
                 UBC 
                 GTCGCAGCCGGGATTTG 
                 259 
                 GCATTGTCAAGTGACGATCACA 
                 260 
               
               
                   
               
            
           
         
       
     
     3. Expression Analysis of Gene Markers by Real-Time PCR 
     (1) Real-Time PCR Using cDNAs of Cells “Without Activation Stimulation” as Templates 
     cDNAs of Th17 cells “without activation stimulation” obtained from samples in the above “1. Preparation of cDNA” were respectively used as a template. The primer sets used were the primer sets for ADAM12, ATP6V0A4, ATP9A, BVES, C5orf40, CDH4, DIO2, L1CAM, MCAM, SHROOM2, TMEM163, UPK1B, DRD2, PGBD5, ODZ4, SLC6A15, AKAP12, C9orf125, POPDC3, UNC13C, PCOLCE2, PNOC, TGFBI, IL1A, BHLHE22, PPARG, SIM1, SNAI2, TBX21, GATA3, FOXP3, CCR6, RORC, GAPDH, ACTB, B2M and UBC, which were designed as described in “2. Design of primer sets”. Real-time PCR was carried out with the template, primer sets and Power SYBR Green PCR Master Mix (Applied Biosystems) in 7300 Real Time PCR System (Applied Biosystems) and Ct value of each gene was measured. PCR was carried out at 50° C. for 2 minutes, 95° C. for 10 minutes followed by 45 cycles of 95° C. for 15 seconds and 60° C. for 1 minute and two cycles of 95° C. for 15 seconds and 60° C. for 1 minute. Ct value was measured by automatic calculation on 7300 Fast SDS software (Applied Biosystems). 
     Real-time PCR was also carried out in the similar manner as above except that cDNAs of Th1 cells “without activation stimulation” obtained from 5 samples, cDNAs of Th2 cells “without activation stimulation” obtained from 5 samples and cDNAs of Treg cells “without activation stimulation” obtained from 4 samples were used as a template instead of cDNAs of Th17 cells “without activation stimulation”, and Ct values for the genes were measured. 
     (2) Real-Time PCR Using cDNAs of Cells “with Activation Stimulation” as Templates 
     cDNAs of Th17 cells “with activation stimulation” obtained from 5 samples in the above “1. Preparation of cDNA” were used as a template. The primer sets used were the primer sets for AKAP12, C9orf125, POPDC3, UNC13C, PCOLCE2, PNOC, TGFBI, IFNG, IL4, IL17A, GAPDH, ACTB, B2M and UBC, which were designed as described in “2. Design of primer sets”. Real-time PCR was carried out with the template, primer sets and Power SYBR Green PCR Master Mix (Applied Biosystems) in 7300 Real Time PCR System (Applied Biosystems) and Ct value of each gene was measured. PCR was carried out at 50° C. for 2 minutes, 95° C. for 10 minutes followed by 45 cycles of 95° C. for 15 seconds and 60° C. for 1 minute and two cycles of 95° C. for 15 seconds and 60° C. for 1 minute. Ct value was measured by automatic calculation on 7300 Fast SDS software (Applied Biosystems). 
     Real-time PCR was also carried out in the similar manner as above except that cDNAs of Th1 cells “with activation stimulation” obtained from 5 samples, cDNAs of Th2 cells “with activation stimulation” obtained from 5 samples and cDNAs of Treg cells “with activation stimulation” obtained from 3 samples were used as a template instead of cDNAs of Th17 cells “with activation stimulation”, and Ct values for the genes were measured. 
     (3) Analysis of Expression Level 
     Based on the Ct values obtained from real-time PCR, expression levels of the gene markers were calculated according to the formula (I):
 
(Expression level of a gene)=100000×2 −y   (I)
 
wherein: y=(Ct value of a gene)−(((Ct value of Gapdh gene)+(Ct value of ACTB gene)+(Ct value of B2M gene)+(Ct value of UBC gene))/4)
 
     The expression level of each gene marker in Th17 cells “without activation stimulation” was obtained as an average of the expression levels of the gene marker in question obtained from five cDNAs used as templates. The expression level of each gene marker in Th17 cells “with activation stimulation” was also obtained as an average of the expression levels of the gene marker in question obtained from five cDNAs used as templates. 
     Similarly, the expression level of each gene marker in Th1 cells or Th2 cells “without activation stimulation” or “with activation stimulation” was obtained as an average of the expression levels of the gene marker in question obtained from five cDNAs used as templates. The expression level of each gene marker in Treg cells “without activation expression” was obtained as an average of the expression levels of the gene marker in question obtained from four cDNAs used as templates. The expression level of each gene marker in Treg cells “with activation stimulation” was obtained as an average of the expression levels of the gene marker in question obtained from three cDNAs used as templates. 
     Expression levels of the gene markers are shown in Tables 13 and 14. Table 13 shows expression levels of gene markers in Th1, Th2, Treg and Th17 cells “without activation stimulation” and Table 14 shows expression levels of gene markers in Th1, Th2, Treg and Th17 cells “with activation stimulation” 
     Expression levels of gene markers in the cells “without activation stimulation” 
     
       
         
           
               
               
             
               
                 TABLE 13 
               
             
            
               
                   
               
               
                 Location of 
                 Expression level 
               
            
           
           
               
               
               
               
               
               
            
               
                 encoded protein 
                 Gene symbol 
                 Th1 
                 Th2 
                 Treg 
                 Th17 
               
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 Membrane 
                 ADAM12 
                 9.95 
                 0.55 
                 22.08 
                 193.83 
               
               
                   
                 ATP6V0A4 
                 35.21 
                 2.55 
                 7.17 
                 625.03 
               
               
                   
                 ATP9A 
                 125.11 
                 9.08 
                 41.42 
                 407.43 
               
               
                   
                 BVES 
                 23.85 
                 3.58 
                 6.84 
                 77.99 
               
               
                   
                 C5orf40 
                 0.74 
                 0.00 
                 33.36 
                 107.84 
               
               
                   
                 CDH4 
                 4.93 
                 7.47 
                 29.44 
                 143.90 
               
               
                   
                 DIO2 
                 0.46 
                 1.25 
                 0.91 
                 10.40 
               
               
                   
                 L1CAM 
                 41.95 
                 45.03 
                 72.77 
                 220.54 
               
               
                   
                 MCAM 
                 62.69 
                 18.93 
                 159.46 
                 500.64 
               
               
                   
                 SHROOM2 
                 0.22 
                 0.46 
                 0.90 
                 11.44 
               
               
                   
                 TMEM163 
                 13.77 
                 8.78 
                 24.25 
                 249.56 
               
               
                   
                 UPK1B 
                 2.94 
                 0.12 
                 0.55 
                 22.59 
               
               
                   
                 DRD2 
                 51.14 
                 49.86 
                 58.21 
                 884.06 
               
               
                   
                 PGBD5 
                 10.30 
                 11.96 
                 19.04 
                 157.52 
               
               
                   
                 ODZ4 
                 1.14 
                 0.44 
                 0.39 
                 41.82 
               
               
                   
                 SLC6A15 
                 0.50 
                 3.46 
                 2.65 
                 27.71 
               
               
                   
                 AKAP12 
                 29.57 
                 30.67 
                 46.71 
                 110.16 
               
               
                   
                 C9orf125 
                 1.31 
                 0.50 
                 3.43 
                 39.73 
               
               
                   
                 POPDC3 
                 0.23 
                 0.00 
                 0.52 
                 10.19 
               
               
                   
                 UNC13C 
                 0.08 
                 0.08 
                 0.27 
                 12.10 
               
               
                 Extracellular/ 
                 PCOLCE2 
                 0.60 
                 0.00 
                 2.59 
                 15.64 
               
               
                 secreted 
                 PNOC 
                 8.01 
                 25.75 
                 5.43 
                 335.81 
               
               
                   
                 TGFBI 
                 58.45 
                 31.18 
                 253.89 
                 1427.38 
               
               
                   
                 IL1A 
                 13.47 
                 47.92 
                 128.89 
                 502.06 
               
               
                 Intracellular 
                 BHLHE22 
                 32.48 
                 13.80 
                 29.69 
                 247.81 
               
               
                   
                 PPARG 
                 120.16 
                 16.40 
                 92.84 
                 456.67 
               
               
                   
                 SIM1 
                 143.63 
                 229.39 
                 40.78 
                 837.78 
               
               
                   
                 SNAI2 
                 0.15 
                 0.03 
                 4.20 
                 69.35 
               
               
                 Known markers 
                 TBX21 
                 4851.97 
                 21.94 
                 513.23 
                 26.92 
               
               
                   
                 GATA3 
                 1820.22 
                 5684.93 
                 4811.71 
                 1353.37 
               
               
                   
                 FOXP3 
                 471.34 
                 250.11 
                 21799.93 
                 334.68 
               
               
                   
                 CCR6 
                 102.73 
                 42.69 
                 939.98 
                 401.01 
               
               
                   
                 RORC 
                 96.77 
                 3.75 
                 328.99 
                 788.05 
               
               
                   
               
            
           
         
       
     
     Expression levels of gene markers in the cells “with activation stimulation 
     
       
         
           
               
               
               
             
               
                 TABLE 14 
               
             
            
               
                   
               
               
                 Location of 
                 Gene 
                 Expression level 
               
            
           
           
               
               
               
               
               
               
            
               
                 encoded protein 
                 symbol 
                 Th1 
                 Th2 
                 Treg 
                 Th17 
               
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 Membrane 
                 AKAP12 
                 34.55 
                 59.13 
                 40.36 
                 201.43 
               
               
                   
                 C9orf125 
                 0.51 
                 0.00 
                 1.92 
                 35.77 
               
               
                   
                 POPDC3 
                 7.28 
                 2.60 
                 3.42 
                 28.09 
               
               
                   
                 UNC13C 
                 0.04 
                 0.36 
                 1.76 
                 11.11 
               
               
                 Extracellular/ 
                 PCOLCE2 
                 1.01 
                 0.36 
                 2.04 
                 20.82 
               
               
                 secreted 
                 PNOC 
                 10.33 
                 28.87 
                 0.63 
                 289.07 
               
               
                   
                 TGFBI 
                 39.99 
                 6.24 
                 86.85 
                 861.02 
               
               
                 Known markers 
                 IFNG 
                 191944.46 
                 393.70 
                 1593.07 
                 1118.25 
               
               
                   
                 IL4 
                 4011.14 
                 8401.51 
                 329.94 
                 108.98 
               
               
                   
                 IL17A 
                 84.43 
                 458.57 
                 1600.38 
                 34052.24 
               
               
                   
               
            
           
         
       
     
     Expression levels of gene markers in Th17 cells and ratios thereof relative to the expression levels of the gene markers in Th1, Th2 and Treg cells are shown in Tables 15 and 16. Table 15 shows expression levels of gene markers in Th17 cells “without activation stimulation” and ratios thereof relative to the expression levels of the gene markers in Th1, Th2 and Treg cells “without activation stimulation”. Table 16 shows expression levels of gene markers in Th17 cells “with activation stimulation” and ratios thereof relative to the expression levels of the gene markers in Th1, Th2 and Treg cells “with activation stimulation”. The values shown in the columns of Th17/Th1, Th17/Th2 and Th17/Treg in Tables 15 and 16 were calculated as follows:
 
 Th 17/ Th 1=(Expression level in  Th 17 cells)/(Expression level in  Th 1 cells)
 
 Th 17/ Th 2=(Expression level in  Th 17 cells)/(Expression level in  Th 2 cells)
 
 Th 17/ Treg =(Expression level in  Th 17 cells)/(Expression level in  Treg  cells)
 
     
       
         
           
               
               
             
               
                 TABLE 15 
               
             
            
               
                   
               
               
                 Location of encoded 
                 Expression ratio 
               
            
           
           
               
               
               
               
               
            
               
                 protein 
                 Gene symbol 
                 Th17/Th1 
                 Th17/Th2 
                 Th17/Treg 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 Membrane 
                 ADAM12 
                 19.49 
                 352.65 
                 8.78 
               
               
                   
                 ATP6V0A4 
                 17.75 
                 245.31 
                 87.13 
               
               
                   
                 ATP9A 
                 3.26 
                 44.86 
                 9.84 
               
               
                   
                 BVES 
                 3.27 
                 21.80 
                 11.41 
               
               
                   
                 C5orf40 
                 144.92 
                 ∞ 
                 3.23 
               
               
                   
                 CDH4 
                 29.17 
                 19.26 
                 4.89 
               
               
                   
                 DIO2 
                 22.83 
                 8.34 
                 11.42 
               
               
                   
                 L1CAM 
                 5.26 
                 4.90 
                 3.03 
               
               
                   
                 MCAM 
                 7.99 
                 26.44 
                 3.14 
               
               
                   
                 SHROOM2 
                 53.13 
                 24.85 
                 12.71 
               
               
                   
                 TMEM163 
                 18.13 
                 28.42 
                 10.29 
               
               
                   
                 UPK1B 
                 7.69 
                 191.37 
                 41.23 
               
               
                   
                 DRD2 
                 17.29 
                 17.73 
                 15.19 
               
               
                   
                 PGBD5 
                 15.30 
                 13.17 
                 8.27 
               
               
                   
                 ODZ4 
                 36.59 
                 94.68 
                 106.41 
               
               
                   
                 SLC6A15 
                 55.24 
                 8.01 
                 10.47 
               
               
                   
                 AKAP12 
                 3.72 
                 3.59 
                 2.36 
               
               
                   
                 C9orf125 
                 30.34 
                 79.90 
                 11.59 
               
               
                   
                 POPDC3 
                 44.01 
                 ∞ 
                 19.75 
               
               
                   
                 UNC13C 
                 152.73 
                 157.50 
                 44.10 
               
               
                 Extracellular/ 
                 PCOLCE2 
                 25.86 
                 4097.03 
                 6.04 
               
               
                 secreted 
                 PNOC 
                 41.93 
                 13.04 
                 61.86 
               
               
                   
                 TGFBI 
                 24.42 
                 45.77 
                 5.62 
               
               
                   
                 IL1A 
                 37.28 
                 10.48 
                 3.90 
               
               
                 Intracellular 
                 BHLHE22 
                 7.63 
                 17.96 
                 8.35 
               
               
                   
                 PPARG 
                 3.80 
                 27.85 
                 4.92 
               
               
                   
                 SIM1 
                 5.83 
                 3.65 
                 20.54 
               
               
                   
                 SNAI2 
                 466.76 
                 2536.05 
                 16.52 
               
               
                 Known markers 
                 TBX21 
                 0.01 
                 1.23 
                 0.05 
               
               
                   
                 GATA3 
                 0.74 
                 0.24 
                 0.28 
               
               
                   
                 FOXP3 
                 0.71 
                 1.34 
                 0.02 
               
               
                   
                 CCR6 
                 3.90 
                 9.39 
                 0.43 
               
               
                   
                 RORC 
                 8.14 
                 210.37 
                 2.40 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
             
               
                 TABLE 16 
               
             
            
               
                   
               
               
                 Location of 
                 Expression ratio 
               
            
           
           
               
               
               
               
               
            
               
                 encoded protein 
                 Gene symbol 
                 Th17/Th1 
                 Th17/Th2 
                 Th17/Treg 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 Membrane 
                 AKAP12 
                 5.83 
                 3.41 
                 4.99 
               
               
                   
                 C9orf125 
                 69.61 
                 ∞ 
                 18.59 
               
               
                   
                 POPDC3 
                 3.86 
                 10.79 
                 8.20 
               
               
                   
                 UNC13C 
                 266.35 
                 31.25 
                 6.30 
               
               
                 Extracellular/ 
                 PCOLCE2 
                 20.54 
                 58.21 
                 10.22 
               
               
                 secreted 
                 PNOC 
                 27.99 
                 10.01 
                 456.13 
               
               
                   
                 TGFBI 
                 21.53 
                 138.01 
                 9.91 
               
               
                 Known markers 
                 IFN-γ 
                 0.01 
                 2.84 
                 0.70 
               
               
                   
                 IL-4 
                 0.03 
                 0.01 
                 0.33 
               
               
                   
                 IL-17A 
                 403.31 
                 74.26 
                 21.28 
               
               
                   
               
            
           
         
       
     
     Table 15 shows that the expression levels of ADAM12, ATP6V0A4, ATP9A, BVES, C5orf40, CDH4, DIO2, L1CAM, MCAM, SHROOM2, TMEM163, UPK1B, DRD2, PGBD5, ODZ4, SLC6A15, AKAP12, C9orf125, POPDC3, UNC13C, PCOLCE2, PNOC, TGFBI, IL1A, BHLHE22, PPARG, SIM1 and SNAI2 in Th17 cells “without activation stimulation” are two or more times higher than that in Th1, Th2 and Treg cells “without activation stimulation”. 
     Table 16 shows that the expression levels of AKAP12, C9orf125, POPDC3, UNC13C, PCOLCE2, PNOC and TGFBI in Th17 cells “with activation stimulation” are two or more times higher than that in Th1, Th2 and Treg cells “with activation stimulation”. 
     Thus, it is demonstrated that these genes are useful as polynucleotide markers for detecting Th17 cells. 
     EXAMPLE 4 
     Expression Analysis of Polynucleotide Markers in Healthy Subjects and Patients with Rheumatoid Arthritis 
     1. Isolation of CD4 Positive Cells from Peripheral Blood of Healthy Subjects and Patients with Rheumatoid Arthritis 
     Peripheral blood from healthy adults (healthy subjects) and patients with rheumatoid arthritis was collected in blood collecting tubes NP-HE0557 (NIPRO) and peripheral blood CD4 positive cells were isolated with magnetic beads bound to anti-CD4 antibody (Miltenyi Biotec). Isolation of CD4 positive cells using anti-CD4 antibody beads was carried out according to the attached instruction. 
     2. Preparation of cDNA from Peripheral Blood CD4 Positive Cells 
     Total RNA was extracted from the isolated peripheral blood CD4 positive cells in the same manner as Example 1, “3. Extraction of total RNA”. The extracted total RNA (0.1 μg) of peripheral blood CD4 positive cells were reverse-transcribed with a poly dT primer (Hokkaido System Science Co., Ltd.), random primers (Hokkaido System Science Co., Ltd.) and Superscript III reverse transcriptase (Invitrogen Corporation) to obtain cDNA of peripheral blood CD4 positive cells. Reverse transcription was carried out according to the attached instructions. 
     The number of samples of peripheral blood CD4 positive cells used for preparation of cDNA is shown in Table 17. 
     
       
         
           
               
               
               
             
               
                 TABLE 17 
               
               
                   
               
               
                   
                 Healthy subject 
                 Patient with rheumatoid arthritis 
               
               
                   
               
             
            
               
                 w/o activation 
                 9 
                 9 
               
               
                 stimulation 
               
               
                   
               
            
           
         
       
     
     3. Expression Analysis of Gene Markers by Real-Time PCR 
     (1) Real-Time PCR Using cDNAs of Peripheral Blood CD4 Positive Cells as Templates 
     cDNAs of peripheral blood CD4 positive cells obtained from nine healthy subjects and nine patients with rheumatoid arthritis as prepared in the above “2. Preparation of cDNA from peripheral blood CD4 positive cells” were used as templates. The primer sets used were the primer sets for ATP6V0A4, BVES, C5orf40, UPK1B, DRD2, PCOLCE2, PNOC, TGFBI, BHLHE22, SIM1, CCR6, RORC, GAPDH, ACTB, B2M, and UBC, which were designed as described in “2. Design of primer sets”. Real-time PCR was carried out with the template, primer sets and Power SYBR Green PCR Master Mix (Applied Biosystems) in 7300 Real Time PCR System (Applied Biosystems) and Ct value of each gene was measured. PCR was carried out at 50° C. for 2 minutes, 95° C. for 10 minutes followed by 45 cycles of 95° C. for 15 seconds and 60° C. for 1 minute and two cycles of 95° C. for 15 seconds and 60° C. for 1 minute. Ct value was measured by automatic calculation on 7300 Fast SDS software (Applied Biosystems). 
     (2) Analysis of Expression Level 
     Expression levels of the gene markers were calculated according to the above formula (I). The expression level of each gene marker in peripheral blood CD4 positive cells of the patients with rheumatoid arthritis was obtained as an average of the expression levels of the gene marker in question obtained from nine cDNAs used as templates. Similarly, the expression level of each gene marker in peripheral blood CD4 positive cells of the healthy subjects was obtained as an average of the expression levels of the gene marker in question obtained from nine cDNAs used as templates. 
     Expression levels of the gene markers in peripheral blood CD4 positive cells from healthy subjects and patients with rheumatoid arthritis and expression ratios of the gene markers between peripheral blood CD4 positive cells of healthy subjects and patients with rheumatoid arthritis are shown in Table 18. In Table 18, “RA” denotes patients with rheumatoid arthritis and “HC” denotes healthy subjects. The values shown in the column RA group/HC group were calculated as follows:
 
 RA  group/ HC  group=(Expression level in peripheral blood  CD 4 positive cells of patients with rheumatoid arthritis)/(Expression level in peripheral blood  CD 4 positive cells of healthy subjects)
 
     
       
         
           
               
               
               
             
               
                 TABLE 18 
               
             
            
               
                   
               
               
                   
                   
                 Expression 
               
               
                   
                   
                 ratio 
               
               
                 Location of encoded 
                 Expression level 
                 RA group/ 
               
            
           
           
               
               
               
               
               
            
               
                 protein 
                 Gene symbol 
                 HC group 
                 RA group 
                 HC group 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 Membrane 
                 ATP6V0A4 
                 6.44 
                 52.16 
                 8.10 
               
               
                   
                 BVES 
                 0.08 
                 32.79 
                 403.57 
               
               
                   
                 C5orf40 
                 0.04 
                 21.60 
                 496.29 
               
               
                   
                 UPK1B 
                 0.31 
                 39.65 
                 126.98 
               
               
                   
                 DRD2 
                 59.42 
                 243.55 
                 4.10 
               
               
                 Extracellular/ 
                 PCOLCE2 
                 0.07 
                 4.94 
                 70.29 
               
               
                 secreted 
                 PNOC 
                 18.89 
                 73.38 
                 3.88 
               
               
                   
                 TGFBI 
                 1651.40 
                 5413.26 
                 3.28 
               
               
                 Intracellular 
                 BHLHE22 
                 3.15 
                 27.75 
                 8.81 
               
               
                   
                 SIM1 
                 4.75 
                 20.73 
                 4.36 
               
               
                 Known markers 
                 CCR6 
                 3136.22 
                 4316.17 
                 1.38 
               
               
                   
                 RORC 
                 528.64 
                 421.20 
                 0.80 
               
               
                   
               
            
           
         
       
     
     Table 18 shows that the expression levels of ATP6V0A4, BVES, C5orf40, UPK1B, DRD2, PCOLCE2, PNOC, TGFBI, BHLHE22 and SIM1 in the RA group were three or more times higher than that in the HC group. This indicates that these genes are useful as polynucleotide markers for screening of patients with rheumatoid arthritis. 
     EXAMPLE 5 
     Analysis of Expression Ratios of Polynucleotide Markers in Cultured Th17 and Th22 Cells Derived from Human Peripheral Blood 
     1. Isolation of Th17 and Th22 Cells from Human Peripheral Blood 
     Buffy coat obtained from peripheral blood of a healthy adult was overlaid on Ficoll-paque plus solution (GE Healthcare Bioscience) and centrifuged to obtain a monocyte fraction. Crude CD4 positive cells were purified from the fraction by using magnetic beads bound to anti-CD4 antibody (Miltenyi Biotec). 
     The obtained CD4 positive cells were stained with the fluorescence labeled antibodies shown in Table 19 and then Th17 and Th22 cells were separated by a cell sorter (FACS Aria: Becton Dickinson). The separation was carried out with the gating shown in Table 20. 
     
       
         
           
               
               
               
               
             
               
                 TABLE 19 
               
               
                   
               
               
                   
                 Fluorescent 
                   
                   
               
               
                 Antigen 
                 labeling substance 
                 Clone 
                 Manufacturer 
               
               
                   
               
             
            
               
                 CD4 
                 APC-Cy7 
                 RPA-T4 
                 BD Biosciences 
               
               
                 CD25 
                 PE-Cy7 
                 BC96 
                 eBioscience 
               
               
                 CXCR3 
                 Alexa Fluor ™ 488 
                 1C6/CXCR3 
                 BD Biosciences 
               
               
                 CCR4 
                 APC 
                 FAB1567A 
                 R&amp;D systems 
               
               
                 CCR6 
                 PE 
                 11A9 
                 BD Biosciences 
               
               
                 CD45RA 
                 APC 
                 HI100 
                 BioLegend 
               
               
                 CCR10 
                 PE 
                 6588-5 
                 BioLegend 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
             
               
                 TABLE 20 
               
               
                   
               
               
                   
                 Cell 
                 Gating 
               
               
                   
               
             
            
               
                   
                 Th17 
                 CD4 high  CD25 low-negative  CXCR3 −  CCR6 +  CCR4 +   
               
               
                   
                 Th22 
                 CD4 high  CD25 low-negative  CD45RA −  CXCR3 −  CCR10 +   
               
               
                   
               
            
           
         
       
     
     The above gating is described in detail in the reference by Acosta-Rodriguez E V et al. (Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells, Nat Immunol., vol. 8, p. 639-646 (2007)). 
     2. Th17 and Th22 Cell Cultures 
     Th17 and Th22 cells derived from adult peripheral blood obtained in the above step 1. were respectively plated in a 96-well plate at the density of 1.5×10 5  cells/0.3 ml/well. The medium used was Yssel medium (IMDM, 1% human serum of AB-type, 0.25% BSA, 1.8 mg/l 2-aminomethanol, 40 mg/l transferrin, 5 mg/l insulin, 2 mg/l linoleic acid, 2 mg/l oleic acid, 2 mg/l palmitic acid, 1% penicillin/streptomycin). 
     For activation and proliferation of the above cells, magnetic beads coated with anti-CD2/3/28 antibody (Miltenyi Biotec) (hereinafter also referred to as “antibody beads”) were added at 0.75×10 5  per well. After addition of cytokines and neutralizing antibodies suitable for differentiation culture of respective Th17 and Th22 cells, cells were incubated in an incubator at 37° C. with 5% CO 2 . Cytokines and neutralizing antibodies used are shown in Table 21. 
     
       
         
           
               
               
               
             
               
                 TABLE 21 
               
               
                   
               
               
                 Cell 
                 Cytokine 
                 Neutralizing antibody (clone) 
               
               
                   
               
             
            
               
                 Th17 
                 TGF-β1, IL-6, IL-23, 
                 Anti-IL-4 antibody (MP4-25D2), 
               
               
                   
                 IL-21, IL-1β, TNFα, IL-2 
                 Anti-IFN-γ antibody (R4-6A2), 
               
               
                 Th22 
                 IL-6, TNFα, IL-2 
                 Anti-IL-4 antibody (MP4-25D2), 
               
               
                   
                   
                 Anti-IFN-γ antibody (R4-6A2), 
               
               
                   
                   
                 Anti-TGFβ antibody (9016) 
               
               
                   
               
            
           
         
       
     
     The concentrations of the above cytokines were 50 ng/ml for IL-6 and 10 ng/ml for other than IL-6. The concentrations of antibodies were 10 μg/ml for anti-IFN-γ antibody, 2.5 μg/ml for anti-IL-4 antibody and 2.5 μg/ml for anti-TGF-β antibody. 
     The cytokines and neutralizing antibodies were obtained from R&amp;D systems and eBioscience, respectively. 
     After three days from the start of culture, cells were diluted three-fold with the medium containing the above cytokines and antibodies and cultured for further seven days (10 days in total). 
     After ten days from the start of culture, the obtained Th17 and Th22 cells were respectively divided into two equal parts, and one was washed with Yssel medium and PBS before centrifugation to collect cells, which were stored at −80° C. until the subsequent RNA extraction step. These cells were designated as Th17 and Th22 cells “without activation stimulation”. The other half was added with the antibody beads and cultured for three more hours to re-activate the cells. The cells were collected by centrifugation and similarly stored at −80° C. These cells were designated as Th17 and Th22 cells “with activation stimulation”. 
     3. Extraction of Total RNA 
     The cells obtained as the above step 2. were subjected to extraction of total RNAs using RNeasy Plus Mini kit and RNeasy micro kit (QIAGEN). The specific procedures were according to the attached instructions of the kits. 
     4. Expression Analysis by Microarray 
     Total RNAs (10 to 100 ng) extracted from the cells as the above step 3. were reverse-transcribed to cDNAs with Two-Cycle Target Labeling and Control Reagents (Affymetrix), and further transcribed to biotinylated-cRNAs. The amplified biotinylated-cRNAs (20 μg) were fragmented. The specific procedures were according to the attached instructions of the kit. 
     The biotinylated-cRNAs derived from the cells as obtained above (15 μg) were applied to GeneChip Human Genome U-133 Plus 2.0 Array (Affymetrix) as samples, transferred to GeneChip Hybridization Oven 640 (Affymetrix) and hybridized under the conditions of 45° C. and 60 rpm for 16 hours. 
     After completion of the hybridization, the microarray was washed and fluorescence-labeled in GeneChip Fluidic Station 450 (Affymetrix), and scanned in GeneChip Scanner 3000 7G (Affymetrix) to obtain fluorescent intensity data. 
     The fluorescent data obtained were standardized with the expression analysis software GeneSpring Ver.11 (Agilent Technologies) based on MAS5 algorithm to obtain relative fluorescent intensities of the genes in the cells. The relative fluorescent intensities correspond to the expression levels of the genes in these cells. 
     Tables 22 and 23 show the results of the relative fluorescent intensities of the genes corresponding to the polynucleotide markers in Th17 cells obtained in Example 1 compared to those in Th22 cells. Table 22 shows expression ratios of the polynucleotide markers in Th17 and Th22 cells “without activation stimulation” and Table 23 shows expression ratios of the polynucleotide markers in Th17 and Th22 cells “with activation stimulation”. In the tables, values in the column “Th17/Th22” correspond to the values obtained by dividing the relative fluorescent intensity of a gene corresponding to a polynucleotide marker in Th17 cells by that in Th22 cells. 
     
       
         
           
               
               
               
             
               
                 TABLE 22 
               
               
                   
               
               
                 Location of encoded 
                   
                 Expression ratio 
               
               
                 protein 
                 Gene symbol 
                 Th22/Th17 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                 Membrane 
                 ADAM12 
                 11.1 
               
               
                   
                 ATP6V0A4 
                 521.3 
               
               
                   
                 ATP9A 
                 33.9 
               
               
                   
                 BVES 
                 3.5 
               
               
                   
                 C5orf40 
                 7.7 
               
               
                   
                 CDH4 
                 12.5 
               
               
                   
                 DIO2 
                 10.6 
               
               
                   
                 MCAM 
                 10.5 
               
               
                   
                 SHROOM2 
                 5.2 
               
               
                   
                 TMEM163 
                 5.6 
               
               
                   
                   
                 3.8 
               
               
                   
                 UPK1B 
                 9.2 
               
               
                   
                 DRD2 
                 5.8 
               
               
                   
                 LOC100134440, PGBD5 
                 14.5 
               
               
                   
                 ODZ4 
                 8.2 
               
               
                   
                 SLC6A15 
                 12.2 
               
               
                   
                 AKAP12 
                 17.2 
               
               
                   
                   
                 36.1 
               
               
                   
                 C9orf125 
                 3.3 
               
               
                 Extracellular/ 
                 PCOLCE2 
                 9.0 
               
               
                 secreted 
                 PNOC 
                 38.5 
               
               
                   
                 TGFBI 
                 182.0 
               
               
                   
                 IL1A 
                 17.7 
               
               
                 Intracellular 
                 BHLHE22 
                 108.3 
               
               
                   
                 PPARG 
                 13.6 
               
               
                   
                 SIM1 
                 4.6 
               
               
                   
                   
                 5.0 
               
               
                   
                 SNAI2 
                 8.2 
               
               
                 Membrane 
                 PTPRM 
                 36.3 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
             
               
                 TABLE 23 
               
               
                   
               
               
                   
                 Location of encoded 
                   
                 Expression ratio 
               
               
                   
                 protein 
                 Gene symbol 
                 Th17/Th22 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 Membrane 
                 AKAP12 
                 12.8 
               
               
                   
                   
                   
                 22.9 
               
               
                   
                   
                 C9orf125 
                 6.8 
               
               
                   
                   
                 POPDC3 
                 5.4 
               
               
                   
                 Extracellular/ 
                 PCOLCE2 
                 11.9 
               
               
                   
                 secreted 
                 PNOC 
                 8.5 
               
               
                   
                   
                 TGFBI 
                 367.4 
               
               
                   
                 Membrane 
                 GPR34 
                 28.2 
               
               
                   
               
            
           
         
       
     
     Tables 22 and 23 clearly indicate that the polynucleotide markers in Th17 cells obtained in Example 1 are expressed three or more times higher in Th17 cells than in Th22 cells. Thus, it is demonstrated that the polynucleotide markers shown in Tables 22 and 23 are useful for detection of Th17 cells.