IL17A
Description
The IL17A (interleukin 17A) is a protein-coding gene located on chromosome 6.
Interleukin-17A is a protein that in humans is encoded by the IL17A gene. In rodents, IL-17A used to be referred to as CTLA8, after the similarity with a viral gene (O40633). The protein encoded by this gene is a proinflammatory cytokine produced by activated T cells. This cytokine regulates the activities of NF-kappaB and mitogen-activated protein kinases. This cytokine can stimulate the expression of IL6 and cyclooxygenase-2 (PTGS2/COX-2), as well as enhance the production of nitric oxide (NO). IL-17A, often referred to as IL-17, was originally discovered at transcriptional level by Rouvier et al. in 1993 from a rodent T-cell hybridoma, derived from the fusion of a mouse cytotoxic T cell clone and a rat T cell lymphoma. Human and mouse IL-17A were cloned a few years later by Yao and Kennedy. Lymphocytes including CD4+, CD8+, gamma-delta T (γδ-T), invariant NKT and innate lymphoid cells (ILCs) are primary sources of IL-17A. Non-T cells, such as neutrophils, have also been reported to produce IL-17A under certain circumstances. IL-17A producing T helper cells (Th17 cells) are a distinct lineage from the Th1 and Th2 CD4+ lineages and the differentiation of Th17 cells requires STAT3 and RORC. IL-17A receptor A (IL-17RA) was first isolated and cloned from mouse EL4 thymoma cells and the bioactivity of IL-17A was confirmed by stimulating the transcriptional factor NF-kappa B activity and interleukin-6 (IL-6) secretion in fibroblasts.
IL-17A is a crucial cytokine in both innate and adaptive immunity, playing a vital role in antimicrobial defense and maintaining tissue integrity. It signals through the IL17RA-IL17RC heterodimeric receptor complex, triggering interactions with the TRAF3IP2 adapter. This initiates downstream activation of NF-kappa-B and MAPkinase pathways via TRAF6, leading to the transcriptional activation of various immune mediators, including cytokines, chemokines, antimicrobial peptides, and matrix metalloproteinases, potentially causing strong inflammation. IL-17A bridges adaptive immunity, mediated by T cells, with acute inflammatory responses, effectively targeting extracellular bacteria and fungi. As a primary effector cytokine of T-helper 17 cells (Th17), it primarily activates and recruits neutrophils to infection and inflammation sites. In the airway epithelium, IL-17A induces chemotaxis of neutrophils by producing CXCL1 and CXCL5 chemokines. In secondary lymphoid organs, it contributes to germinal center formation by regulating the chemotactic response of B cells to CXCL12 and CXCL13, enhancing B cell retention within these centers, increasing B cell somatic hypermutation rates, and promoting plasma cell selection. IL-17A also serves as an effector cytokine for a subset of gamma-delta T cells, functioning within an inflammatory circuit downstream of IL1B, TLR2, and IL23A-IL12B to enhance neutrophil recruitment for efficient bacterial clearance. It acts as an effector cytokine for innate immune cells, including invariant natural killer cells (iNKT) and group 3 innate lymphoid cells, mediating initial neutrophilic inflammation. IL-17A is crucial for maintaining the integrity of epithelial barriers during both normal conditions and pathogen infection. In acute injury, it directly contributes to epithelial barrier formation by regulating OCLN localization and tight junction biogenesis. As part of the mucosal immune response triggered by commensal bacteria, IL-17A enhances host resistance to pathogenic bacterial and fungal infections by promoting neutrophil recruitment and antimicrobial peptide release. In synergy with IL17F, IL-17A mediates the production of antimicrobial beta-defensins DEFB1, DEFB103A, and DEFB104A by mucosal epithelial cells, limiting microbial entry through epithelial barriers. IL-17A is involved in antiviral defense through various mechanisms. It enhances immunity against West Nile virus by promoting T cell cytotoxicity. IL-17A may play a beneficial role in influenza A virus (H5N1) infection by enhancing B cell recruitment and immune response in the lung. It contributes to influenza A virus (H1N1) clearance by driving the differentiation of B-1a B cells, leading to the production of virus-specific IgM antibodies at the first line of host defense. {ECO:0000250|UniProtKB:Q62386, ECO:0000269|PubMed:17911633, ECO:0000269|PubMed:18684971, ECO:0000269|PubMed:19825828, ECO:0000269|PubMed:21350122, ECO:0000269|PubMed:24120361, ECO:0000269|PubMed:8676080}
IL17A is also known as CTLA-8, CTLA8, IL-17, IL-17A, IL17, ILA17.
