IL17A

Interleukin 17A (IL-17A) is a pro-inflammatory cytokine in the IL-17 family, encoded by the IL17A gene in humans. It is produced by various immune cells, most notably T helper 17 (Th17) cells, but also γδ T cells, natural killer T cells, and innate lymphoid cells type 3. IL-17A is secreted mainly as a homodimer and can form IL-17A/IL-17F heterodimers with IL-17F. It acts at mucosal surfaces to promote inflammation and host defense against extracellular bacteria and fungi.

IL-17A signals through a receptor complex composed of IL-17 receptor A (IL-17RA) and IL-17RC on target cells. Binding recruits the adaptor protein ACT1 (TRAF3IP2) and activates downstream pathways such as NF-κB, MAPKs, and C/EBP, leading to transcription of pro-inflammatory genes. These include chemokines CXCL1, CXCL2, and CCL20; cytokines such as IL-6 and GM-CSF; and antimicrobial peptides, promoting neutrophil recruitment and granulopoiesis.

In immunity, IL-17A is a key effector of the Th17 axis. IL-23–driven differentiation of Th17 cells and subsequent IL-17A production help coordinate mucosal defenses but can also drive chronic inflammatory responses when dysregulated.

Dysregulated IL-17A signaling has been implicated in autoimmune and inflammatory diseases, including psoriasis, psoriatic arthritis, rheumatoid arthritis, axial spondyloarthritis, inflammatory bowel disease, and certain asthma phenotypes. Therapeutic blockade of IL-17A reduces disease activity in several of these conditions.

Clinical applications include monoclonal antibodies secukinumab and ixekizumab that neutralize IL-17A, and bimekizumab that inhibits IL-17A and IL-17F. Side effects can include increased susceptibility to mucosal candidiasis due to impaired IL-17–mediated mucosal immunity. Response to therapy is variable across diseases and patients.