IL-17F induces inflammation, dysfunction and cell death in mouse islets

Catterall, T., Fynch, S., Kay, T. W. H., Thomas, H. E. & Sutherland, A. P. R. (2020). IL-17F induces inflammation, dysfunction and cell death in mouse islets. Scientific Reports, 10 (1), https://doi.org/10.1038/s41598-020-69805-2.

Access Status

Open Access

Abstract

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.

Publisher Licence

CC BY

Publisher URL

https://doi.org/10.1038/s41598-020-69805-2

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Biochemistry and Pharmacology - Research Publications
Medicine (St Vincent's) - Research Publications
Minerva Elements Records