bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cartilage remodeling genes on murine chromosome 15 involved in sex-affected pathways controlling the effector phase of arthritis (88.19)
Authors: Adarichev Vyacheslav , Kudryavtseva Elena 
Published: January 2023

Abstract
Gender differences in susceptibility to many autoimmune diseases including rheumatoid arthritis (RA) are well documented. To dissect sex-affected inflammatory mechanisms in murine models for RA, we generated BALB/c.DBA/2-Pgia8 congenic strain. The strain carries chromosome 15 sex-specific locus Pgia8 that controls arthritides induced with aggrecan, collagen type II, B. burgdorferi, and pristane. We report here that the locus also controls collagen antibody-induced arthritis (CAIA), which stresses the locus role in the effector inflammatory phase of the disease. CAIA severity in congenic males was 30% lower (p &lt; 0.005) than in wild-type BALB/c males (locus effect). Severity in congenic males was only 50% of that in congenic females (sex-related effect). Differential expression analysis of total RNA isolated from paws showed that only dozen of genes within the locus were differentially expressed in wild-type versus congenic mice, and their expression was significantly affected by sex. In inflammatory conditions, expression pattern for the gene encoding for Cthrc1 (collagen triple helix repeat containing) was highly correlated with CAIA severity, r=0.84. In basal conditions, Cthrc1 expression correlated with the concentration of IL-6 message. Taken together, these data could indicate that Cthrc1 controls cartilage remodeling differently in males and females and might provide a converging point for regulation of different types of arthritides including RA.
FCGR genetics in HIV disease (88.21)
Authors: Poonia Bhawna , Pauza David 
Published: January 2023

Abstract
Antibody-dependent cellular cytotoxicity (ADCC) is a mechanism for HIV-specific antibodies to target infected cells for destruction by cytotoxic effectors. The Fc portion of IgG antibodies binds cytotoxic effector cells through a family of Fc receptors that include FCGR3A (CD16). Antibody binding to Fc receptor also delivers an activating signal to the effector cells. Thus there is a balance between effector cell stimulation and target cell killing during ADCC. Single nucleotide polymorphisms (SNP) in the Fc receptor gene FCGR3A alter the amino acid sequence and encode high or low functioning proteins. We predicted that HIV elite controller groups would have increased frequencies of the high functioning allele compared to HIV progressors or uninfected controls. Genomic DNA was analyzed from individuals with no HIV infection, Elite controllers and HIV progressors on HAART for polymorphism rs396991, that results in a T (F amino acid) or a G (V amino acid) allele at the SNP position. PCR was used to amplify a region of FCGR3A and an analysis of rs396991 was done using the ABISnapshot multiplex kit. An allele frequency of T/G 0.82/0.18 for normal donors, T/G 0.75/0.25 for elite controllers and T/G 0.58/0.42 for HIV progressors was found. These results of higher frequencies of high functioning alleles in HIV progressors suggest that this allele may be responsible for chronic lymphocyte activation that is a feature of progressing HIV disease.
Developmental Regulation of Immunoglobulin CDR-H3 Content through Control of DH and JH Usage in Mice (88.4)
Authors: Szymanska Ewa , Schelonka Robert , Vale Andre , Zhuang Yingxin , Gartland G. , Schroeder, Jr. Harry 
Published: January 2023

Abstract
The ability to generate antibodies to specific antigens develops in a controlled, programmed fashion during ontogeny. This process occurs in parallel with the regulated development of antibody repertoire diversity. Compared to adult, the human fetal antibody repertoire is enriched for use of most DH-proximal VH gene segment. The CDR-H3 repertoire is depleted of N nucleotides and enriched for DQ52, the most JH-proximal DH; and for DH-proximal JH2 and 3. The murine fetal antibody repertoire is also enriched for the use of the most DH proximal VH gene segment and depleted of N nucleotides. However, the extent to which DH and JH usage is controlled is unclear. We used surface expression of CD43, BP-1, CD19, IgM and IgD to sort B lineage cells from BALB/cJ perinatal liver, then used RT-PCR to amplify VH7183-containing VDJCμ transcripts. We observed increased use of JH-proximal, DHQ52 and DH-proximal JH2 at all stages of development. Patterns of VH7183-DH-JH usage and CDR-H3 content during B cell development in 18 day fetal liver and neonatal liver were compared to those of adult bone marrow. When evaluated by length and hydrophobicity, evidence of CDR-H3 repertoire selection was most evident in the transition from Hardy Fraction C to D. Our results indicate that regulation of the antibody repertoire ontogeny in mouse shares more similarities with human than previously appreciated. Supported by NIH AI48115.
Neutrophil gelatinase-associated lipocalin (NGAL): Endogenous activators of the immune system (89.15)
Authors: Tewary Poonam , Redmond Chris , Clifton Mathew , Yang De , Oppenheim Joost 
Published: January 2023

Abstract
Neutrophil gelatinase-associated lipocalin (NGAL), also known as Lipocalin 2 (Lcn2), is a member of the extremely diverse family of molecules called lipocalins. Recent studies have shown that NGAL is secreted by multiple cell types including neutrophils, and has a wide variety of functions from anti-apoptotic signaling to kidney development. We have been investigating the properties of four different forms of NGAL to determine whether they exhibit the characteristics of an alarmin. Alarmins are endogenous antimicrobial peptides or proteins which are released in response to tissue injury or infection and have the additional capacity to recruit and activate antigen presenting cells (APCs) and enhance antigen specific immune responses in vivo. Our results show that different variants of NGAL are potent stimulants of antigen presenting cells. Treatment of monocyte-derived iDCs with NGAL induced their maturation as evidenced by upregulated surface markers (CD80, CD83, CD86, and MHC class II), enhanced production of cytokines (IL-6, CXCL8, IL-12p70, and TNF alpha), and acquisition of the capacity to stimulate allogeneic T cell proliferation. Thus, NGAL can rapidly mobilize and activate pro-inflammatory innate immune responses and by generating mature DCs can also induce adaptive immune responses. If these NGAL molecules are shown to induce a significant immune response, they may prove to be useful as non-toxic vaccine adjuvants for treatment of various types of tumors.
Recognition of bacterial formyl peptides by FPR2 (89.21)
Authors: Southgate Erica , Nanamori Masakatsu , Ye Richard 
Published: January 2023

Abstract
Formyl peptide receptor 2 (FPR2) is a homologue to FPR1, which is known for its high-affinity binding to the E. coli-derived chemotactic peptide fMet-Leu-Phe (fMLF). Unlike FPR1, FPR2 is a low affinity receptor for fMLF, raising questions for its role in host defense. We found that FPR2 is able to respond to a variety of formylated peptides with activation of cellular functions. A pentapeptide fMet-Ile-Val-Ile-Leu from L. monocytogenes and a tetrapeptide fMet-Ile-Phe-Leu from S. aureus were ~ 100 fold more potent than fMLF in activating FPR2 suggesting that bacterial formyl peptides can be high affinity ligands for FPR2. The presence of the formyl group at the N-terminus and C-terminal interaction are both important for full activation of FPR2. In comparison, FPR1 activation through formyl peptides only requires interaction with the N-terminal formyl group. We also investigated the role of charged residues in ligand interactions of both FPR1 and FPR2 receptors. Mutation of residues 84, 85 and 284 in each receptor were not competent to effect formyl peptide activation for each receptor, however; the specificity by FPR2 agonists was directly affected in the mutational study, indicating involvement of these residues in structure conformation and downstream signaling. These data demonstrate a divergent role for FPR2 in recognizing bacterial and synthetic formyl peptides, suggesting a potential function of this receptor in host defense as well as homeostatic regulation.
Effect of lipoteichoic acid on B cells in female C57BL/6 mice (89.25)
Authors: Dasgupta Subhajit , Molano Ivan , Eudaly Jackie , Baker DeAnna , Cunningham Mellissa , Gilkeson Gary 
Published: January 2023

Abstract
Activation of B cells is hall mark of protective immune responses against pathogens. A wide range of antigen(s) and differences in mode of recognition of these antigens confer diversified adaptive immune responses in infection, autoimmune disease like lupus or in allergy. Our initial observations via flow cytometry indicated a shift in CD19+ B cells in spleens of female C57BL/6 mice injected TLR2 ligand LTA via the intraperitoneal route as compared to control mice received sterile PBS. The spleen cells of LTA injected mice demonstrated a population of CD19+ B cells which also found to express TLR2 (0.2% CD19+TLR2+) as compared with control (0.1% CD19+ TLR2+ cells). We also detected a small population of CD19+CD25+ cells in spleens of LTA injected mice as compared with control. There was considerable alteration in CD19+CD40+ cell population in LTA injected mice as compared with control. Our observations demonstrated a shift in CD19+CD86+ activated B cell populations in LTA injected mice. Selective estrogen receptor alpha antagonist MPP was found to alter the B cell activation markers in LTA mice indicating possible role of estrogen receptor alpha in B cell activation. The observations indicate salient role of TLR2 ligands on B cell activation signals that may in turn, responsible for regulation of adaptive immune responses.
CD34+CD31+ immature myeloid cells (IMC) as an inhibitor cell on the production of antimicrobial peptide: II. Glycyrrhizin inhibits IMC suppressor cell activities (89.27)
Authors: Yoshida Shohei , Asai Akira , Inatsu Akihito , Kobayashi Makiko , Herndon David , Suzuki Fujio 
Published: January 2023

Abstract
In the accompanying paper I, CD34+CD31+ IMC are shown to be inhibitory on HBD-1 production by normal human epidermal keratinocytes (NHEK). CCL2 and IL-10 released from CD34+CD31+ IMC are identified as effectors in this suppressor cell activity. In this study, the suppressor cell activity of CD34+CD31+ IMC was shown to be controlled by glycyrrhizin (GL), an active component of licorice root. CD34+CD31+ IMC were isolated from peripheral blood of exercised donors, as described in the accompanying paper I. These IMC were transwell-cultured with NHEK for 48 hrs in the presence or absence of GL (Minophagen Pharmaceutical Co., Ltd., Tokyo, Japan), and cells in the bottom chamber (NHEK) were assayed for HBD-1 mRNA expression by RT-PCR. Also, the production of CCL2 and IL-10 by CD34+CD31+ IMC (1 x 106 cells/ml) treated with GL was measured by ELISA. In the results, NHEK transwell-cultured with CD34+CD31+ IMC did not express HBD-1 mRNA, while these transwell-cultures were performed with GL (10-100 μg/ml), HBD-1 mRNA was expressed by NHEK. The production of CCL2 and IL-10 was greatly reduced in CD34+CD31+ IMC cultures added with GL. These results indicate that the suppressor cell activity of CD34+CD31+ IMC on HBD-1 production by NHEK is controlled by GL. This study was supported by SHC #8610.
Human L-ficolin can bind and defence against multiple pathogens (89.29)
Authors: Zhang Xiao-Lian , A.M. Ali Mohammed , Luo Fengling , Wang Qilong , He Ruifen , Shen Xihui , Yang Rongge 
Published: January 2023

Abstract
Human L-ficolin is a recently identified lectin complement pathway activator present in normal plasma and inplicated to be associated with infectious diseases, but little is known about the roles of ficolins in the infections of human important pathogens. In this study, we firstly demonstrate that human L-ficolin can bind and reduce infectivity of Human Immunodeficiency Virus (HIV), Hepatitis C virus (HCV), Mycobacteria tuberculosis (M.tb) and Salmonella typhimurium C5 in vitro or in vivo. Further investigations demonstrated C-terminal of L-ficolin specifically bound to these microbial carbohydrates, thereby activate lectin complement pathway and complement mediated cytolytic activity. Our findings support the development of L-ficolin as a novel innate immune molecule immunotherapy against the infections of these important pathogens.
CD34+CD31+ immature myeloid cells (IMC) as an inhibitor cell on the production of antimicrobial peptide: I. Inhibitory activities of CD34+CD31+ IMC on the antimicrobial peptide production by keratinocytes (89.31)
Authors: Jones Vickie , Yoshida Shohei , Kobayashi Makiko , Herndon David , Suzuki Fujio 
Published: January 2023

Abstract
CD34+CD31+ IMC, isolated from peripheral blood of exercised donors, are shown to be inhibitor cells on HBD-1 production by normal human epidermal keratinocytes (NHEK). Lineage cell-depleted PBMC were isolated from peripheral blood of healthy donors 24 hrs after 1-hr of treadmill exercise using a lineage cell depletion kit, then CD34+CD31+ IMC were sorted from these cells by flow cytometry. IMC were transwell-cultured with NHEK for 48 hrs, and NHEK harvested were analyzed for HBD-1 mRNA expression by RT-PCR. Also, conditioned media harvested 48 hrs after the cultivation of CD34+CD31+ IMC (IMC-culture media) were assayed for their inhibitory activities on HBD-1 production by NHEK. In the results, HBD-1 mRNA expression by NHEK was completely inhibited after transwell-cultivation with CD34+CD31+ IMC. HBD-1 was not detected in NHEK cultures supplemented with 20 to 40% of IMC-culture media. IL-10 and CCL2 were detected in the IMC-culture media. When NHEK were cultured with the IMC-culture media previously treated with a mixture of anti-CCL2 and anti-IL-10 mAbs, HBD-1 was produced in their culture fluids. These results indicate that CD34+CD31+ IMC transiently appearing in peripheral blood of exercised donors are inhibitory on HBD-1 production by NHEK. CCL2 and IL-10 produced by these cells are required on the CD34+CD31+ IMC-mediated inhibition of HBD-1 production by NHEK. This study was supported by SHC #8610.
Natural polysaccharides and nucleic acid based TLR ligand nanocomplexes improves immune response (89.41)
Authors: Tincer Gizem , Yerlikaya Seda , Gürsel Ihsan 
Published: January 2023

Abstract
Toll-like receptors (TLR) induce NF-κB dependent or independent cytokine/chemokine secretion and contribute to the establishment of innate and adaptive immune response. When nucleic acid ligands were given in vivo they were attacked by endonucleases and have low uptake efficiency into immune cells due to premature adsorption to serum proteins. Polysaccharides (PS) from edible mushrooms were characterized as immunostimulatory amphiphilic macromolecules. Due to their β-glucan moieties, we have established that these PS`s are recognized and induce TLR2 (but not via NOD-1 or NOD2) mediated activation (as evidenced by NO, TNFα IL6 responses) and can be naturally targeted through this extracellular receptor. Next, we complexed PS with pI:C, R848 and CpG ODN, a TLR3,7/8, and 9 ligands. Different ratio of these nanocomplexes displayed a strong synergism as evidenced by a Th1-biased cytokine secretion and NO production compared to their alone counterparts. This study showed that natural PS is an immunostimulatory compound by itself, and furthermore, it could be used to effectively complex and deliver nucleic acid based TLR ligands to relevant immune cells. The targeted delivery of the generated nanocomplexes led to a more pronounced immune activation that is not achievable either of the stimulants when given alone.
Identification of novel ligand(s) for the NK cell receptor, KIR2DL4 (89.44)
Authors: Brusilovsky Michael , Porgador Angel , Campbell Kerry 
Published: January 2023

Abstract
The ligands for many NK cell activating receptors remain unknown, and identification of these ligands has become a major goal for understanding the molecular basis of NK cell activation. The killer Ig-like receptor (KIR) 2DL4 is the only NK cell receptor that triggers cytokine production (IFNγ, chemokines, pro-angiogenic factors), but not cytotoxicity in resting NK cells. Several early studies reported that 2DL4 recognizes the non-classical MHC-I molecule - HLA-G. We have recently found that a soluble form of 2DL4 binds to various tumor cell lines of epithelial or fibroblast origin that lack HLA-G expression, but not to transformed hematopoietic or HLA-G positive lines. Our results demonstrate that soluble forms of HLA-G and HLA-A are both recognized by the soluble 2DL4, but binding of the 2DL4 to cell surface forms of HLA-G or HLA-A was not detected. Our studies further suggest that soluble 2DL4 or MHC-I molecules may exhibit interactions that are not characteristic of cell surface proteins and that 2DL4 recognition of the tumor cell lines is independent of surface expression of MHC-I or MHC-I like molecules.
Distinct Roles of Rab27a in Lytic Granule Movement at the Plasma Membrane and in the Cytosol (89.47)
Authors: Liu Dongfang , Meckel Tobias , Long Eric 
Published: January 2023

Abstract
The small GTPase Rab27a is essential for degranulation by cytotoxic T cells and natural killer (NK) cells. To test its role in granule movement we visualized lytic granules in live, unstimulated NK cells by high-speed 3-dimensional (3D) spinning disc confocal and 2-dimensional (2D) total internal reflection fluorescence (TIRF) microscopy. Movement was tracked and quantified by automated image analysis of thousands of granules. Pharmacological inhibitors showed that long-range, directed 3D movement required microtubules (MT) but not actin, whereas 2D movement under the plasma membrane required actin dynamics. The role of Rab27a was examined by shRNA-mediated knockdown in a human NK cell line and by using NK cells from Rab27a-mutant Ashen mice. Fewer lytic granules reached the plasma membrane in the absence of Rab27a. Rab27a promoted actin-dependent, directed movement under the plasma membrane. In contrast, Rab27a reduced tracking along MT and diffusion of lytic granules in the cytosol. Therefore, Rab27a promotes delivery of lytic granules to, and movement at the plasma membrane, and has a distinct role in the cytosol, where it serves as tether to constrain lytic granule movement.
Vitamin C attenuates ERK signaling induced by LL-37 in human dermal fibroblasts (89.5)
Authors: Kim Hee Jung , Choi Jung Min , Cho Baik Kee , Cho Dae Ho , Park Hyun Jeong 
Published: January 2023

Abstract
Vitamin C (ascorbic acid), a water-soluble micronutrient present in fruits and vegetables, is important for multiple biological functions. Vitamin C is used as an anti-aging agent because of its collagen enhancing effects. The precise cellular signaling mechanism of vitamin C is not well known. Here we investigate the profibrotic mechanism of vitamin C against LL-37. Antimicrobial peptide LL-37 decreases collagen expression at mRNA and protein levels in human dermal fibroblasts (HDFs). The ability of LL-37 to inhibit collagen expression is dependent on phosphorylation of extracellular signal-regulated kinase (ERK). HDFs were treated with vitamin C before 2 hours of LL-37 treatment. Vitamin C, at 0.5mM concentration, enhances collagen mRNA expression and total soluble collagen production inhibited by LL-37. H2O2 decreased the expression of COL1A1, COL1A2, and COL3A1 mRNA, as was collagen production. We found that collagen expression and production reduced by LL-37 were increased by N-acetyl-L-cysteine (NAC). These results indicate that ROI levels are involved in collagen expression. Furthermore, vitamin C turned off phosphorylation of ERK that was induced by LL-37. Ets-1 transcriptional factor, which is involved in the regulation of collagen expression by LL-37, was also inhibited by vitamin C. This study shows that vitamin C enhances collagen production by inhibiting the ERK pathway induced by LL-37.
MHC class I polymorphism defines NK cell-mediated resistance to murine cytomegalovirus (89.50)
Authors: Brown Michael , Xie Xuefang , Stadnisky Michael , Bullock Timothy , Coats Ebony 
Published: January 2023

Abstract
NK cells are vital to innate antiviral defenses; NK deficiency corresponds to susceptibility to infection, inflammation, tissue damage, and mortality. In MA/My mice, NK-mediated resistance to murine (M)CMV infection requires H-2k, but a critical gene has not been identified. We mapped the resistance effect to the MHC class I (MHC-I) D locus. A cloned Dk transgene was microinjected into MCMV-susceptible (MA/My.L-H2b x C57L)F1 embryos. MHC-I Dk founders were backcrossed to MA/My.L-H2b or C57L mice. We found that transgenic MHC-I Dk expression conferred MCMV resistance. Ly49G+ NK cells were required since their removal before infection abrogated resistance. Using bone marrow chimeras, a requirement for MHC-I Dk expression in hematopoietic or non-hematopoietic cells was found essential to full MCMV resistance. MHC-I Dk resistance through Ly49G+ NK cells further corresponded to splenic CD11c+ dendritic cell stability and acquisition of virus-specific CD8+ T cells after infection. We conclude that MHC-I Dk is essential to MCMV resistance and define a role for MHC-I Dk on both hematopoietic and non-hematopoietic cells in enhancing NK virus control and virus-specific immunity.
Enhancement of antiviral immunity by a peptide antagonist of SOCS (89.9)
Authors: Ahmed Chulbul , Dabelic Rea , Johnson Howard 
Published: January 2023

Abstract
Suppressors of cytokine signaling (SOCS) are negative regulators of both innate and adaptive immunity via inhibition of signaling by cytokines such as interferons (IFNs). We have developed a small peptide antagonist of SOCS-1 that corresponds to the activation loop of the Janus kinase JAK2. SOCS-1 inhibits both type I and type II IFN activities by binding to the kinase activation loop via the kinase inhibitory region (KIR) of the SOCS. The antagonist, pJAK2(1001-1013), inhibited the replication of vaccinia virus and EMC virus in cell culture, suggesting that it possesses broad antiviral activity. In addition, pJAK2(1001-1013) protected mice against lethal vaccinia and EMC virus infection. pJAK2(1001-1013) increased the intracellular level of the constitutive IFNβ, which may play a role in the antagonist antiviral effect at the cellular level. pJAK2(1001-1013) also synergizes with IFNs as per IFN gamma mimetic to exert a multiplicative antiviral effect at the level of transcription, the cell, and protection of mice against lethal viral infection. pJAK2(1001-1013) binds to the KIR of both SOCS-1 and SOCS-3 and blocks their inhibitory effects on the GAS promoter. In addition to a direct antiviral effect and synergism with IFN, the SOCS antagonist also exhibits adjuvant effects on the humoral and cellular arms as well as an enhancement of polyI:C activation of TLR3. The SOCS antagonist thus presents a novel and effective approach to enhancement of host defense against viruses.