Interleukin‐17A deficiency ameliorates streptozotocin‐induced diabetes

Summary 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.