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Interleukin 17F (IL-17F) homodimer is a pro-inflammatory cytokine belonging to the IL-17 family, primarily produced by Th17 cells, γδ T cells, and innate lymphoid cells [UniProt, NIH]. It signals through a heteromeric receptor complex composed of IL-17RA and IL-17RC, activating downstream pathways such as NF-κB and MAPK to induce the expression of chemokines (e.g., CXCL1, CXCL8) and other inflammatory mediators [Immunity, PubMed]. While IL-17F shares structural homology with IL-17A, it is often expressed at significantly higher levels in inflamed tissues, such as psoriatic skin and synovial fluid, contributing to the chronicity and severity of inflammation in autoimmune diseases [NIH, BioDrugs]. Therapeutically, the IL-17F homodimer is a key target in the treatment of chronic immune-mediated inflammatory diseases. Dual inhibitors like bimekizumab, which neutralize both IL-17A and IL-17F, have demonstrated superior clinical efficacy in achieving skin clearance and joint symptom relief compared to agents targeting IL-17A alone [Psoriasis Hub, NIH]. However, because IL-17F plays a vital role in host defense against extracellular pathogens, its inhibition is associated with an increased risk of mucosal fungal infections, most notably oral candidiasis [Frontiers in Immunology, NIH].
Neutralization of IL-17F homodimers to prevent binding to the IL-17RA/IL-17RC receptor complex, thereby inhibiting downstream pro-inflammatory signaling pathways such as NF-κB, MAPK, and Act1-mediated cascades [NIH, Immunity].
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