interleukin17A

Interleukin-17A (IL-17A) is a pro-inflammatory cytokine in the IL-17 family. It is produced by several immune cell types, most notably CD4+ T helper 17 (Th17) cells, but also gamma-delta T cells, innate lymphoid cells, neutrophils, and macrophages. The IL-17A gene is in the IL-17 gene cluster on chromosome 6 and encodes a homodimeric protein that drives inflammation.

It signals through a receptor complex of IL-17RA and IL-17RC. Binding recruits the adaptor ACT1 and activates NF-κB and MAPK pathways, inducing transcription of pro-inflammatory cytokines (e.g., IL-6, TNF), chemokines (e.g., CXCL1/2/8), and antimicrobial peptides. IL-17A often acts with IL-1β and TNF to amplify responses.

Biologically, IL-17A promotes neutrophil recruitment, stimulates antimicrobial peptide production by epithelial and stromal cells, and enhances mucosal barrier defenses. It is important for defense against extracellular bacteria and fungi at barrier sites such as skin, lung, and gut.

Dysregulated IL-17A signaling is linked to autoimmune and inflammatory diseases, including psoriasis, psoriatic arthritis, ankylosing spondylitis, rheumatoid arthritis, inflammatory bowel disease, and multiple sclerosis. Elevated IL-17A is detected in lesional tissues and fluids in these conditions.

Therapies targeting IL-17A or its receptor are approved for several IL-17–driven diseases. Anti-IL-17A antibodies include secukinumab and ixekizumab; anti-IL-17RA antibody is brodalumab; newer agents such as bimekizumab target IL-17A and IL-17F. Adverse effects include higher risk of mucocutaneous candidiasis and infections.

Research goals include using IL-17A as a biomarker of inflammatory activity and further defining its roles in host defense, tissue homeostasis, and the balance between protective immunity and autoimmunity.