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Interleukin-17F (IL-17F) is a pro-inflammatory cytokine and a member of the IL-17 family, primarily produced by Th17 cells, γδ T cells, and innate lymphoid cells [UniProt Q96PD4]. It exists as a homodimer or as a heterodimer with IL-17A, signaling through a receptor complex composed of IL-17RA and IL-17RC subunits [Gaffen, S. L., Nature Reviews Immunology, 2009]. This signaling pathway induces the expression of various chemokines and pro-inflammatory cytokines, which facilitate neutrophil recruitment and tissue inflammation [Tang, C., et al., Cytokine, 2018]. In the intestinal tract, IL-17F plays a dual role; it is essential for mucosal defense against extracellular pathogens, yet its overproduction is strongly linked to the pathogenesis of inflammatory bowel diseases (IBD), including Crohn's disease and ulcerative colitis [Monin, L., & Gaffen, S. L., Cold Spring Harbor Perspectives in Biology, 2018]. Elevated intestinal expression of IL-17F is a characteristic feature of active inflammation in these patients [Monin, L., & Gaffen, S. L., 2018]. Consequently, IL-17F is a key therapeutic target in autoimmune and inflammatory disorders [UCB Pharma, 2023]. Drugs such as bimekizumab, which dual-inhibits both IL-17A and IL-17F, have shown significant efficacy in treating conditions like psoriasis and are being investigated for IBD [ClinicalTrials.gov, 2024]. Therapeutic targeting of IL-17F aims to reduce the chronic inflammatory response while potentially maintaining some of the protective functions associated with IL-17A [Monin, L., & Gaffen, S. L., 2018].
Neutralization of the IL-17F cytokine to prevent its interaction with the IL-17RA/IL-17RC receptor complex, thereby inhibiting pro-inflammatory signaling pathways.
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