IL17F gene

The IL17F gene (IL17F stands for "Interleukin-17F") is a protein-coding gene located on chromosome 6p12.2. The protein encoded by the IL17F gene is a cytokine. Member of the interleukin-17 family. It has sequence similarity to IL17A. It is expressed by activated T cells and has been shown to stimulate the production of several other cytokines, including IL6, IL8, and CSF2/GM-CSF. Furthermore, this cytokine inhibits endothelial cell angiogenesis and stimulates endothelial cells to produce IL2, TGFB1/TGFB, and monocyte chemoattractant protein-1.

Diseases associated with IL17F include.

Familial chronic mucocutaneous candidiasis, type 6 (see also below chronic mucocutaneous candidiasis (classification).

Related pathways include cytokine signaling pathways in the immune system.

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.

1. Aggor FEY et al (2020) Oral epithelial IL-22/STAT3 signaling licenses IL-17-mediated immunity to oral mucosal candidiasis. Sci Immunol 5(48):eaba0570.
2. Puel A et al. (2011) Chronic mucocutaneous candidiasis in humans with inborn errors of interleukin-17 immunity. Science 332: 65-68.