Recombinant Human Interleukin-17F protein (IL17F)

Function

Effector cytokine of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity (PubMed:21350122). IL17A-IL17F signals via IL17RA-IL17RC heterodimeric receptor complex, triggering homotypic interaction of IL17RA and IL17RC chains with TRAF3IP2 adapter through SEFIR domains. This leads to downstream TRAF6-mediated activation of NF-kappa-B and MAPkinase pathways ultimately resulting in transcriptional activation of cytokines, chemokines, antimicrobial peptides and matrix metalloproteinases, with potential strong immune inflammation (PubMed:11574464, PubMed:11591732, PubMed:11591768, PubMed:17911633, PubMed:18684971, PubMed:21350122, PubMed:28827714). IL17A-IL17F is primarily involved in host defense against extracellular bacteria and fungi by inducing neutrophilic inflammation (By similarity). As signature effector cytokine of T-helper 17 cells (Th17), primarily induces neutrophil activation and recruitment at infection and inflammatory sites (By similarity). Stimulates the production of antimicrobial beta-defensins DEFB1, DEFB103A, and DEFB104A by mucosal epithelial cells, limiting the entry of microbes through the epithelial barriers (By similarity). IL17F homodimer can signal via IL17RC homodimeric receptor complex, triggering downstream activation of TRAF6 and NF-kappa-B signaling pathway (PubMed:32187518). Via IL17RC induces transcriptional activation of IL33, a potent cytokine that stimulates group 2 innate lymphoid cells and adaptive T-helper 2 cells involved in pulmonary allergic response to fungi. Likely via IL17RC, promotes sympathetic innervation of peripheral organs by coordinating the communication between gamma-delta T cells and parenchymal cells. Stimulates sympathetic innervation of thermogenic adipose tissue by driving TGFB1 expression (By similarity). Regulates the composition of intestinal microbiota and immune tolerance by inducing antimicrobial proteins that specifically control the growth of commensal Firmicutes and Bacteroidetes (By similarity)

Subcellular Location

Secreted

Disease Association

Candidiasis, familial, 6 (CANDF6) : A primary immunodeficiency disorder with altered immune responses and impaired clearance of fungal infections, selective against Candida. It is characterized by persistent and/or recurrent infections of the skin, nails and mucous membranes caused by organisms of the genus Candida, mainly Candida albicans. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Expressed in T-helper 1 and T-helper 2 cells, basophils and mast cells

Subunit

Homodimer; disulfide-linked (PubMed:19838198, PubMed:32187518). Heterodimer with IL17A (IL17A-IL17F) (PubMed:17355969). Forms complexes with IL17RA and IL17RC receptors with 2:1 binding stoichiometry: two receptor chains for one interleukin molecule. IL17F homodimer forms predominantly complexes with IL17RC homodimer, whereas IL17A-IL17F favors complexes with IL17RA-IL17RC (PubMed:17911633, PubMed:18684971, PubMed:28827714, PubMed:32187518). IL17RA and IL17RC chains cannot distinguish between IL17A and IL17F molecules, potentially enabling the formation of topologically distinct complexes (PubMed:28827714)

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• Kawaguchi M. et al. Identification of a novel cytokine, ML-1, and its expression in subjects with asthma. — J. Immunol. (2001)
• Zhang Z. et al. Signal peptide prediction based on analysis of experimentally verified cleavage sites. — Protein Sci. (2004)
• Wright J.F. et al. Identification of an interleukin 17F/17A heterodimer in activated human CD4+ T cells. — J. Biol. Chem. (2007)
• Kuestner R.E. et al. Identification of the IL-17 receptor related molecule IL-17RC as the receptor for IL-17F. — J. Immunol. (2007)
• Wright J.F. et al. The human IL-17F/IL-17A heterodimeric cytokine signals through the IL-17RA/IL-17RC receptor complex. — J. Immunol. (2008)