IL17

IL-17 refers to a family of pro-inflammatory cytokines, with IL-17A being the best characterized. Members of the IL-17 family include IL-17A through IL-17F, which can form homodimers or, for IL-17A and IL-17F, a heterodimer IL-17A/F. IL-17A and IL-17F are the most prominent in humans and are often studied together for their overlapping yet distinct roles in inflammation.

Source and regulation: IL-17 cytokines are primarily produced by T helper 17 (Th17) cells, but are also made by γδ T cells, innate lymphoid cells, neutrophils, and other cell types. Th17 differentiation is driven by cytokines such as TGF-β, IL-6, and IL-23, with transcriptional control by RORγt. IL-17 production is tightly regulated, and dysregulation can contribute to pathological inflammation.

Receptor and signaling: IL-17A and IL-17F signal through a receptor complex that includes IL-17RA and IL-17RC. Binding recruits the adaptor protein Act1 and activates downstream NF-κB and MAPK pathways, leading to expression of pro-inflammatory cytokines, chemokines (for example CXCL1, CXCL8/IL-8, CCL20), and growth factors. This promotes neutrophil recruitment and amplifies inflammatory responses, often in synergy with TNF-α and IL-1β.

Role in health and disease: IL-17 plays a protective role in mucosal and barrier immunity against extracellular bacteria and fungi. However, excessive IL-17 signaling is linked to autoimmune and inflammatory diseases, including psoriasis, psoriatic arthritis, axial spondyloarthritis, inflammatory bowel disease, and multiple sclerosis. Therapeutic inhibition of IL-17 signaling has become an effective strategy in several of these conditions.

Therapeutics and safety: Anti-IL-17 therapies include monoclonal antibodies targeting IL-17A (e.g., secukinumab, ixekizumab) and IL-17RA (e.g., brodalumab). Bi-specific or dual IL-17A/F inhibitors (e.g., bimekizumab) are also in use. While effective, IL-17 blockade can increase susceptibility to mucocutaneous candidiasis and may carry other infection risks; long-term safety continues to be monitored.