Interleukin‐17A deficiency ameliorates streptozotocin‐induced diabetes |
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| Authors: | Zan Tong Weihuang Liu Huichao Yan Chen Dong |
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| Affiliation: | 1. School of Basic Medical Sciences, Wuhan University, Wuha, China;2. Zhongshan Hospital of Hubei Province, Wuha, China;3. School of Medicines, Tsinghua University, Beijing, China |
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| 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. |
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| Keywords: | diabetes interleukin‐17A myeloid‐derived suppressor cells streptozotocin |
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