Protein: Interleukin-17A (IL-17) (IL-17A) (Cytotoxic T-lymphocyte-associated antigen 8) (CTLA-8) (Q62386)
Organism: Mus musculus (Mouse)
Function: Effector cytokine of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity. Signals via IL17RA-IL17RC heterodimeric receptor complex, triggering homotypic interaction of IL17RA and IL17RC chains with TRAF3IP2 adapter. This leads to downstream TRAF6-mediated activation of NF-kappa-B and MAPkinase pathways ultimately resulting in transcriptional activation of cytokines, chemokines, antimicrobial peptides and matrix metalloproteinases, with potential strong immune inflammation. Plays an important role in connecting T cell-mediated adaptive immunity and acute inflammatory response to destroy extracellular bacteria and fungi. As a signature effector cytokine of T-helper 17 cells (Th17), primarily induces neutrophil activation and recruitment at infection and inflammatory sites. In airway epithelium, mediates neutrophil chemotaxis via induction of CXCL1 and CXCL5 chemokines. In secondary lymphoid organs, contributes to germinal center formation by regulating the chemotactic response of B cells to CXCL12 and CXCL13, enhancing retention of B cells within the germinal centers, B cell somatic hypermutation rate and selection toward plasma cells. Effector cytokine of a subset of gamma-delta T cells that functions as part of an inflammatory circuit downstream IL1B, TLR2 and IL23A-IL12B to promote neutrophil recruitment for efficient bacterial clearance. Effector cytokine of innate immune cells including invariant natural killer cell (iNKT) and group 3 innate lymphoid cells that mediate initial neutrophilic inflammation. Involved in the maintenance of the integrity of epithelial barriers during homeostasis and pathogen infection. Upon acute injury, has a direct role in epithelial barrier formation by regulating OCLN localization and tight junction biogenesis. As part of the mucosal immune response induced by commensal bacteria, enhances host's ability to resist pathogenic bacterial and fungal infections by promoting neutrophil recruitment and antimicrobial peptides release. In synergy with IL17F, mediates the production of antimicrobial beta-defensins DEFB1, DEFB103A, and DEFB104A by mucosal epithelial cells, limiting the entry of microbes through the epithelial barriers. Involved in antiviral host defense through various mechanisms. Enhances immunity against West Nile virus by promoting T cell cytotoxicity. May play a beneficial role in influenza A virus (H5N1) infection by enhancing B cell recruitment and immune response in the lung. Contributes to influenza A virus (H1N1) clearance by driving the differentiation of B-1a B cells, providing for production of virus-specific IgM antibodies at first line of host defense.
Subcellular location: Secreted {ECO:0000269|PubMed:18025225}.
Sequence: MSPGRASSVSLMLLLLLSLAATVKAAAIIPQSSACPNTEAKDFLQNVKVNLKVFNSLGAKVSSRRPSDYLNRSTSPWTLHRNEDPDRYPSVIWEAQCRHQRCVNAEGKLDHHMNSVLIQQEILVLKREPESCPFTFRVEKMLVGVGCTCVASIVRQAA
InterPro domains: - IPR010345: Interleukin-17 family (family) [73-150]
- IPR020440: Interleukin-17, chordata (family) [75-150]
- IPR029034: Cystine-knot cytokine (homologous_superfamily) [26-157]
Interaction partners: - Interleukin-17 receptor C
- Interleukin-17 receptor A
- Interferon gamma
- Interleukin-10
- Interleukin-6
- Interleukin-17F
- Interleukin-22
- T-cell surface glycoprotein CD4
- Interleukin-4
- Signal transducer and activator of transcription 3
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005515 (protein binding), GO:0042802 (identical protein binding), GO:0005102 (signaling receptor binding), GO:0046983 (protein dimerization activity), GO:0042803 (protein homodimerization activity), GO:0005126 (cytokine receptor binding), GO:0046982 (protein heterodimerization activity)
Biological Process (BP): GO:0008150 (biological process), GO:0065007 (biological regulation), GO:0048518 (positive regulation of biological process), GO:0050896 (response to stimulus), GO:0050789 (regulation of biological process), GO:0009987 (cellular process), GO:0042221 (response to chemical), GO:0019222 (regulation of metabolic process), GO:0009719 (response to endogenous stimulus), GO:0048522 (positive regulation of cellular process), GO:0050794 (regulation of cellular process), GO:0009893 (positive regulation of metabolic process), GO:0051716 (cellular response to stimulus), GO:0001101 (response to acid chemical), GO:0010942 (positive regulation of cell death), GO:0010941 (regulation of cell death), GO:1901698 (response to nitrogen compound), GO:0010604 (positive regulation of macromolecule metabolic process), GO:0031325 (positive regulation of cellular metabolic process), GO:0070887 (cellular response to chemical stimulus), GO:0009889 (regulation of biosynthetic process), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0071495 (cellular response to endogenous stimulus), GO:0060255 (regulation of macromolecule metabolic process), GO:0031323 (regulation of cellular metabolic process), GO:1901700 (response to oxygen-containing compound), GO:0080090 (regulation of primary metabolic process), GO:0010033 (response to organic substance), GO:0009725 (response to hormone), GO:0009891 (positive regulation of biosynthetic process), GO:0051173 (positive regulation of nitrogen compound metabolic process), GO:0010557 (positive regulation of macromolecule biosynthetic process), GO:0045935 (positive regulation of nucleobase-containing compound metabolic process), GO:0051254 (positive regulation of RNA metabolic process), GO:0032870 (cellular response to hormone stimulus), GO:0043200 (response to amino acid), GO:0010243 (response to organonitrogen compound), GO:0010556 (regulation of macromolecule biosynthetic process), GO:0071310 (cellular response to organic substance), GO:0033993 (response to lipid), GO:0010940 (positive regulation of necrotic cell death), GO:0031326 (regulation of cellular biosynthetic process), GO:0048545 (response to steroid hormone), GO:0019219 (regulation of nucleobase-containing compound metabolic process), GO:0014070 (response to organic cyclic compound), GO:0051252 (regulation of RNA metabolic process), GO:0031328 (positive regulation of cellular biosynthetic process), GO:0010468 (regulation of gene expression), GO:0010939 (regulation of necrotic cell death), GO:0071383 (cellular response to steroid hormone stimulus), GO:1902680 (positive regulation of RNA biosynthetic process), GO:0031960 (response to corticosteroid), GO:2001141 (regulation of RNA biosynthetic process), GO:0006355 (regulation of DNA-templated transcription), GO:0071407 (cellular response to organic cyclic compound), GO:0071396 (cellular response to lipid), GO:0006357 (regulation of transcription by RNA polymerase II), GO:0045893 (positive regulation of DNA-templated transcription), GO:1903508 (positive regulation of nucleic acid-templated transcription), GO:1903506 (regulation of nucleic acid-templated transcription), GO:0051384 (response to glucocorticoid), GO:0071384 (cellular response to corticosteroid stimulus), GO:0045944 (positive regulation of transcription by RNA polymerase II), GO:0071385 (cellular response to glucocorticoid stimulus)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005576 (extracellular region), GO:0005615 (extracellular space)