title: 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.
authors.affiliation: School of Basic Medical Sciences, Wuhan University, Wuha, China.
authors.forename: Zan
authors.initials: Z
authors.lastname: Tong
authors.affiliation: School of Basic Medical Sciences, Wuhan University, Wuha, China.
authors.forename: Weihuang
authors.initials: W
authors.lastname: Liu
authors.affiliation: Zhongshan Hospital of Hubei Province, Wuha, China.
authors.forename: Huichao
authors.initials: H
authors.lastname: Yan
authors.affiliation: School of Medicines, Tsinghua University, Beijing, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Dong
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D039481:CD11b Antigen / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D018920:Coculture Techniques; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D007328:Insulin / Q000097:blood; D020381:Interleukin-17 / Q000172:deficiency* / Q000235:genetics; D008213:Lymphocyte Activation; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D010179:Pancreas / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D019707:Receptors, Chemokine / Q000276:immunology / Q000378:metabolism; D013154:Spleen / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D039481:CD11b Antigen; C503133:Gr-1 protein, mouse; C098680:Il17a protein, mouse; D007328:Insulin; D020381:Interleukin-17; D019707:Receptors, Chemokine
keywords: diabetes; interleukin-17A; myeloid-derived suppressor cells; streptozotocin