Interleukin-17A deficiency ameliorates streptozotocin-induced diabetes

Abstract

Interleukin-17 (IL-17) is a cytokine with critical functions in multiple autoimmune diseases. However, its roles in type I diabetes and the underlying mechanisms remain to be fully elucidated. In the current study, we investigated the impact of IL-17 deficiency on streptozotocin (STZ) -induced diabetes. Il-17-/- mice exhibited attenuated hyperglycaemia and insulitis after STZ treatment compared with control mice. The Il-17-/- mice had fewer CD8+ cells infiltrating the pancreas than wild-type controls after STZ injection. Wild-type mice showed increased percentage and number of splenic CD8+ cells and decreased Gr1+ CD11b+ myeloid-derived suppressor cells (MDSC) after STZ treatment, but Il-17-/- mice maintained the percentages and numbers of splenic CD8+ cells and MDSC, suggesting that IL-17 is implicated in STZ-induced cellular immune responses in the spleen. We further purified the MDSC from spleens of STZ-treated mice. Il-17-/- MDSC showed increased ability to suppress CD8+ cell proliferation in vitro compared with wild-type MDSC. Transfer of MDSC to diabetic mice showed that MDSC from Il-17-/- mice could ameliorate hyperglycaemia. Moreover, recipients with MDSC from Il-17-/- mice had a decreased percentage of CD8+ cell in the spleen compared with recipients with MDSC from wild-type mice. These data suggest that IL-17 is required in splenic MDSC function after STZ delivery. In summary, our study has revealed a pathogenic role of IL-17 in an STZ-induced diabetes model with important implications for our understanding of IL-17 function in autoimmune diseases.