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Interleukin‐17A deficiency ameliorates streptozotocin‐induced diabetes
Author(s) -
Tong Zan,
Liu Weihuang,
Yan Huichao,
Dong Chen
Publication year - 2015
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12512
Subject(s) - insulitis , streptozotocin , cd8 , spleen , immune system , endocrinology , medicine , interleukin 17 , t cell , diabetes mellitus , adoptive cell transfer , cytokine , type 1 diabetes , immunology
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 CD 8 + cells infiltrating the pancreas than wild‐type controls after STZ injection. Wild‐type mice showed increased percentage and number of splenic CD 8 + cells and decreased Gr1 + CD 11b + myeloid‐derived suppressor cells ( MDSC ) after STZ treatment, but Il‐17 −/− mice maintained the percentages and numbers of splenic CD 8 + 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 CD 8 + 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 CD 8 + 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.