TY - JOUR TI - IL-17F induces inflammation, dysfunction and cell death in mouse islets AU - Catterall, Tara AU - Fynch, Stacey AU - Kay, Thomas W. H. AU - Thomas, Helen E. AU - Sutherland, Andrew P. R. T2 - Scientific Reports AB - Type 17 immune responses, typified by the production of the cytokines IL-17A and IL-17F, have been implicated in the development of type 1 diabetes in animal models and human patients, however the underlying pathogenic mechanisms have not been clearly elucidated. While previous studies show that IL-17A enhances inflammatory gene expression and cell death in mouse β-cells and human islets, the function of IL-17F in pancreatic β-cells is completely untested to date. Here we show that IL-17F exhibits potent pathogenic effects in mouse β-cell lines and islets. IL-17F signals via the IL-17RA and -RC subunits in β-cells and in combination with other inflammatory cytokines induces expression of chemokine transcripts, suppresses the expression of β-cell identity genes and impairs glucose stimulated insulin secretion. Further IL-17F induces cell death in primary mouse islets. This occurs via Jnk, p38 and NF-κB dependent induction of Nos2 and is completely ablated in the presence of an inducible nitric oxide synthase (iNOS) inhibitor. Together these data indicate that IL-17F possesses similar pathogenic activities to IL-17A in mouse β-cell lines and islets and is likely to be a type 17 associated pathogenic factor in type 1 diabetes. DA - 2020/08/04/ PY - 2020 DO - 10.1038/s41598-020-69805-2 DP - www.nature.com VL - 10 IS - 1 SP - 13077 LA - en SN - 2045-2322 UR - https://www.nature.com/articles/s41598-020-69805-2 Y2 - 2020/08/04/21:18:13 ER -