Interleukin-17F is an effector cytokine of the innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity. The cytokine belongs to the interleukin-17 familyIL17F(and IL17A) acts through a heterodimeric IL17RA-IL17RC receptor complex that triggers a homotypic interaction of IL17RA and IL17RC chains with the TRAF3IP2 adaptor via SEFIR domains. This leads to downstream TRAF6-mediated activation of NF-kappa-B and MAP kinase signaling pathways, ultimately resulting in transcriptional activation of cytokines, chemokines, antimicrobial peptides, and matrix metalloproteinases, generally leading to severe immune inflammation.
IL-17A/IL-17F are primarily involved in host defense against extracellular bacteria and fungi, by triggering neutrophilic inflammation.
As a characteristic effector cytokine of T helper 17 cells (Th17), interleukin-17F primarily induces neutrophil activation and recruitment at sites of infection and inflammation. The cytokine stimulates the production of the antimicrobial beta-defensins DEFB1, DEFB103A, and DEFB104A by mucosal epithelial cells, which prevent microbial invasion through the epithelial barrier. Via IL17RC, IL-17F induces transcriptional activation of IL33, a potent cytokine that stimulates group 2 innate lymphoid cells and adaptive T helper 2 cells involved in the allergic response to fungi in the lung. It probably promotes sympathetic innervation of peripheral organs via IL17RC by coordinating communication between gamma-delta T cells and parenchymal cells. Thus, it also regulates the composition of the gut microbiota and immune tolerance by inducing antimicrobial proteins that specifically control the growth of certain commensals.