Interleukin-17A deficiency ameliorates streptozotocin-induced diabetes
Interleukin-17A deficiency ameliorates streptozotocin-induced diabetes
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DOI：
10.1111/imm.12512
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发表时间：
2015-10-01
期刊：
影响因子：
6.4
通讯作者：
Dong，Chen
中科院分区：
文献类型：
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作者：
Tong，Zan;Liu，Weihuang;Dong，Chen
白细胞介素-17（IL-17）是一种细胞因子，在多种自身免疫性疾病中具有重要功能。然而，其在I型糖尿病中的作用及其潜在机制仍有待充分阐明。在当前的研究中，我们研究了IL-17缺乏对链脲佐菌素（STZ）诱导的糖尿病的影响。与对照小鼠相比，IL-17−/−小鼠在STZ治疗后表现出减轻的高血糖和胰岛炎。在注射STZ后，IL-17−/−小鼠胰腺浸润的CD 8+细胞比野生型对照少。野生型小鼠在STZ治疗后脾脏CD 8+细胞的百分比和数量增加，Gr 1 + CD 11b+髓源性抑制细胞（MDSC）减少，但IL-17−/−小鼠保持了脾脏CD 8+细胞和MDSC的百分比和数量，表明IL-17与STZ诱导的脾脏细胞免疫应答有关。我们进一步从STZ处理的小鼠脾脏中纯化了MDSC。与野生型MDSC相比，IL-17−/−MDSC在体外显示出更强的抑制CD 8+细胞增殖的能力。将MDSC转移到糖尿病小鼠表明，来自IL-17−/−小鼠的MDSC可以改善高血糖症。此外，与来自野生型小鼠的MDSC受体相比，来自IL-17−/−小鼠的MDSC受体脾脏中CD 8+细胞的百分比降低。这些数据表明，IL-17是STZ递送后脾脏MDSC功能所必需的。总之，我们的研究揭示了IL-17在STZ诱导的糖尿病模型中的致病作用，这对我们理解IL-17在自身免疫性疾病中的功能具有重要意义。
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. TheIl‐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, butIl‐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 proliferationin vitrocompared with wild‐type MDSC. Transfer of MDSC to diabetic mice showed that MDSC fromIl‐17−/−mice could ameliorate hyperglycaemia. Moreover, recipients with MDSC fromIl‐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.