Preventative role of interleukin-17 producing regulatory T helper type 17 (Treg17) cells in type 1 diabetes in non-obese diabetic mice
Preventative role of interleukin-17 producing regulatory T helper type 17 (Treg17) cells in type 1 diabetes in non-obese diabetic mice
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DOI：
10.1111/cei.12691
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发表时间：
2015-12-01
影响因子：
4.6
通讯作者：
Singh, B.
中科院分区：
文献类型：
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作者：
Bellemore, S. M.;Nikoopour, E.;Singh, B.
17 型辅助 T (Th17) 细胞已被证明在自身免疫性疾病中具有致病性；然而，它们在 1 型糖尿病 (T1D) 中的作用仍无定论。我们发现来自BDC25 T细胞受体转基因非肥胖糖尿病（NOD）小鼠的CD4（+）T细胞可以在白细胞介素（IL）-23+IL-6的驱动下进行Th17分化，产生大量的IL-22，并且这些细胞在过继移植后诱导年轻NOD小鼠发生T1D。相反，用转化生长因子 (TGF)-+IL-6 极化这些细胞会产生非糖尿病性调节性 Th17 (T(reg)17) 细胞，这些细胞表达高水平的芳烃受体 (AhR) 和 IL-10，但产生的 IL-22 水平大大降低。通过在年轻 NOD 小鼠而非 NOD 严重联合免疫缺陷 (SCID) 小鼠中进行过继转移研究，评估了这些 Th17 亚群的致糖尿病潜力，以防止这些细胞在体内可能发生的转分化。根据我们的结果，我们建议在适当的极化条件下，CD4(+) T 细胞可以产生致病性 Th17 细胞和非致病性调节性 T(reg)17 细胞。这或许可以解释 Th17 细胞在 T1D 中的矛盾作用。产生 IL-17 的 T(reg)17 细胞为调节自身免疫提供了一种新型的调节性 T 细胞群。
T helper type 17 (Th17) cells have been shown to be pathogenic in autoimmune diseases; however, their role in type 1 diabetes (T1D) remains inconclusive. We have found that Th17 differentiation of CD4(+) T cells from BDC25 T cell receptor transgenic non-obese diabetic (NOD) mice can be driven by interleukin (IL)-23+IL-6 to produce large amounts of IL-22, and these cells induce T1D in young NOD mice upon adoptive transfer. Conversely, polarizing these cells with transforming growth factor (TGF)-+IL-6 led to non-diabetogenic regulatory Th17 (T(reg)17) cells that express high levels of aryl hydrocarbon receptor (AhR) and IL-10 but produced much reduced levels of IL-22. The diabetogenic potential of these Th17 subsets was assessed by adoptive transfer studies in young NOD mice and not NOD.severe combined immunodeficient (SCID) mice to prevent possible transdifferentiation of these cells in vivo. Based upon our results, we suggest that both pathogenic Th17 cells and non-pathogenic regulatory T(reg)17 cells can be generated from CD4(+) T cells under appropriate polarization conditions. This may explain the contradictory role of Th17 cells in T1D. The IL-17 producing T(reg)17 cells offer a novel regulatory T cell population for the modulation of autoimmunity.