IL-17F induces inflammation, dysfunction and cell death in mouse islets
Tara Catterall, Stacey Fynch, Thomas WH Kay, Helen E Thomas, Andrew PR Sutherland
SCIENTIFIC REPORTS | NATURE PUBLISHING GROUP | Published : 2020
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 che..View full abstract
Awarded by National Health and Medical Research Council of Australia (NHMRC)
We thank Joby Trigg, Yohana Akang, Rhiannon Greaves, Vicki Moshovakis and Elissa Tonkin (St Vincent's Hospital, Australia) for excellent technical assistance and animal husbandry. This work was supported by a National Health and Medical Research Council of Australia (NHMRC) project grant (APP1071350), program grant (APP1037321) and fellowship (H.E.T.). A.P.R.S. is supported by a Juvenile Diabetes Research Foundation (JDRF) Career Development Award and Diabetes Australia Millennium Award. St Vincent's Institute receives support from the Operational Infrastructure Support Scheme of the Government of Victoria.