Genetic deletion of IL-17 suppresses the progression to diabetes in the NOD mice in the Age-dependent fashion

辅助性T细胞17型（Th 17）已被证明在几种自身免疫性疾病的小鼠模型中发挥重要作用，这些疾病以前被认为是Th 1-显性的。然而，在NOD小鼠中，IL-17/Th 17的相关性仍然是有争议的，因为它们固有的可塑性。来源于BDC2.5 NOD小鼠的Th 17细胞通过体内转化为Th 1细胞来转移糖尿病。我们在此研究了IL-17单缺陷或IL-17/IFN-γ受体双缺陷对NOD小鼠胰岛炎/糖尿病发展的影响。IL-17单缺陷显著延迟糖尿病的发作并减轻胰岛炎的严重程度，但IL-17缺陷小鼠中直至50周龄的糖尿病累积发病率与野生型（wt）小鼠相似。来自年轻的非糖尿病IL-17单缺陷NOD小鼠的CD 4 + CD 25-T细胞的连续转移研究，而不是来自老年小鼠的连续转移研究，表明与来自相应的wt-小鼠的那些相比，受体NOD-Scid小鼠中的疾病也显著延迟。另一方面，IL-17/IFN-γ受体双缺陷显着抑制糖尿病的发展，尽管单缺陷和双缺陷小鼠之间的胰岛素炎水平相似。提示IL-17/Th 17在NOD小鼠胰岛炎的发生发展中起重要作用，Th 1-Th 17细胞的相互作用促进了糖尿病的发生发展。

T helper type 17(Th17) cells have been shown to play important roles in mouse models of several autoimmune diseases that had previously been thought Th1-dominant. In the NOD mouse, however, the relevance of IL-17/Th17 is still controversial, because of their inherent plasticity. Th17 cells derived from BDC2.5 NOD mice transfer diabetes through conversion to Th1 cells in vivo. We here studied the impact of IL-17 single-deficiency or IL-17/IFN-γreceptor double-deficiency on the development of insulitis/diabetes in NOD mice. IL-17 single-deficiency significantly delayed the onset of diabetes and attenuated the severity of insulitis, but the cumulative incidence of diabetes until 50 weeks of age in IL-17 deficient mice was similar to that in wild-type(wt) mice. Adoptive transfer study with CD4+CD25-T cells from young non-diabetic IL-17 single-deficient NOD mice, but not that from older mice showed also significantly delayed disease in the recipient NOD-Scid mice as compared with those from the corresponding wt-mice. On the other hand, IL-17/IFN-γreceptor double-deficiency significantly suppressed the development of diabetes, although the levels of insulitis were similar between single-deficient and double-deficient mice. These results indicate that IL-17/Th17 plays a significant role in the development of insulitis in pre-diabetic NOD mice and the interaction of Th1-Th17 cells contributes to diabetes development.