Anti-IL-17A

Interleukin-17A (IL-17A), also known as CTLA-8, is a 15-20 kDa glycosylated cytokine that plays an important role in anti-microbial and chronic inflammation. The six IL-17 cytokines (IL-17A-F)are encoded by separate genes but adopt a conserved cystine knot fold. Mature rat IL-17A shares 60% and 89% amino acid sequence identity with human and mouse IL-17A, respectively. IL-17A is secreted by Th17 cells, gamma /delta T cells, iNKT cells, NK cells, LTi cells, neutrophils, and intestinal Paneth cells. It forms disulfide-linked homodimers as well as disulfide-linked heterodimers with IL-17F. IL-17A exerts its effects through the transmembrane IL-17RA in complex with IL-17RC or IL-17RD. Both IL-17RA and IL-17RC are required for responsiveness to heterodimeric IL-17A/F. IL-17A promotes protective mucosal and epidermal inflammation in response to microbial infection. It induces chemokine production, neutrophil influx, and the production of antibacterial peptides. IL-17A/F likewise induces neutrophil migration, but IL-17F does not. IL-17A additionally enhances the production of inflammatory mediators by rheumatoid synovial fibroblasts and contributes to TNF-alpha induced shock. In contrast, it can protect against the progression of colitis by limiting chronic inflammation. IL-17A encourages the formation of autoreactive germinal centers and exacerbates the onset and progression of experimental models of autoimmunity. IL-17A has been shown to exert either tumorigenic or anti-tumor effects. Protein function: Effector cytokine of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity (PubMed:18025225, PubMed:19144317, PubMed:26431948). 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 (PubMed:16200068, PubMed:17911633, PubMed:19144317, PubMed:26431948). 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 (PubMed:18025225). In airway epithelium, mediates neutrophil chemotaxis via induction of CXCL1 and CXCL5 chemokines (PubMed:18025225, PubMed:27923703). 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 (PubMed:18157131). 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 (PubMed:17372004, PubMed:20364087, PubMed:28709803). Effector cytokine of innate immune cells including invariant natural killer cell (iNKT) and group 3 innate lymphoid cells that mediate initial neutrophilic inflammation (PubMed:17470641, PubMed:23255360). 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 (PubMed:26431948). 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 (PubMed:28709803). 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 (PubMed:19144317). Involved in antiviral host defense through various mechanisms (PubMed:21946434, PubMed:26735852, PubMed:27795421). Enhances immunity against West Nile virus by promoting T cell cytotoxicity (PubMed:27795421). May play a beneficial role in influenza A virus (H5N1) infection by enhancing B cell recruitment and immune response in the lung (PubMed:21946434). 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 (PubMed:26735852). [The UniProt Consortium]