Alt. symbols: IL-17F | ML-1 | ML1

Approved name: interleukin 17F
Alt. names: interleukin17F | cytokine ML1

Location: 6p12.2: 52236681 - 52245689 (-)
Gene type: protein_coding, 3 transcripts.

Scores: LoFtool: 0.587000 | pLI: 0.03027393 | LOEUF: 1.179

HGNC: 16404

NCBI: 112744, RefSeq: NG_031869.1

Ensembl: ENSG00000112116.11

LRG_356 | Status: public

OMIM: 606496

Expression | ProteinAtlas

IL17F is a signature effector cytokine of T-helper 17 cells (Th17), a type of CD4+ T cell involved in host protection against bacterial and fungal infections as well as in orchestration of chronic inflammation and autoimmunity in many organs. IL-17 signaling is important for inducing neutrophilic inflammation and maintaining tissue integrity in response to extracellular pathogens. Activation of the IL17RA-IL17RC receptors by IL-17A and/or IL-17F leads to downstream TRAF6-mediated activation of NF-kappaB and MAPK pathways, leading to transactivation of cytokines, chemokines, antimicrobial peptides and matrix metalloproteinases. It has also been implicated in regulation gastrointestinal immune tolerance via control of microbiome composition and pulmonary allergic responses to fungi. Th17 cells produce interleukin (IL)-17A and variable amounts of IL-17F, IL-21, IL-22 and IL-26, under the regulation of retinoic-acid-related orphan receptors (ROR)-γt and ROR-α. Accumulating evidence implicates Th17 cells in the tissue-damaging immune response seen in both major forms of inflammatory bowel disease (IBD) – ulcerative colitis and Crohn’s disease - but Th17 cells also have tissue-protective effects via enhancement of epithelial barrier function and immune regulatory mechanisms.

One heterozygous missense variant (S65L) in IL17F has been reported for autosomal dominant chronic mucocutaneous candidiasis [OMIM: 613956] with incomplete clinical penetrance; affected patients had normal IgM and normal to slightly high IgG levels (PMID: 21350122). Functional studies suggested a hypomorphic, dominant-negative effect of this mutation, whereby receptor-binding and bioactivity of both IL-17F homodimers and IL-17A/IL-17F heterodimers were impaired. Another rare heterozygous missens e variant (T85I) was reported in a 32-year-old woman with diagnosis of CVID at age 22, featuring a history of pneumonias and gastrointestinal issues. She showed decreased levels of class-switched B cells and naïve CD4+ and CD8+ T cells; immunoglobulin levels and functional studies were not reported (PMID: 32047491). In a Chinese study of 270 ulcerative colitis (UC) patients, 82 Crohn’s disease (CD) patients and 268 healthy controls, an IL17F variant (rs763780 or c.482A>G; p.His161Arg) was associated with increased risk for CD development (P = 0.033, OR 1.18, 95% confidence interval (CI) 1.41–3.04) and also correlated weakly with the age of UC onset (P = 0.05, OR 0.97, 95% CI 0.94–1.00) (PMID: 23652560). However, in another study of 499 CD patients, 216 UC patients, and 967 controls, the same IL17F variant was observed with similar frequencies in IBD patients and controls and was only weakly associated with low body mass index (BMI; P = 0.009) and an earlier age of disease onset (P = 0.039) in UC. These authors did find, however, that intestinal IL-17F mRNA expression was 4.4-fold increased in active CD lesions compared to uninflamed colonic biopsies (P = 0.016). [Load More]