Appropriate balance of T helper 17 (Th17) and regulatory T (Treg) cells maintains immune tolerance and host defense. Disruption of Th17-Treg cell balance is implicated in a number of immune-mediated diseases, many of which display dysregulation of the insulin-like growth factor (IGF) system. Here, we show that, among effector T cell subsets, Th17 and Treg cells selectively expressed multiple components of the IGF system. Signaling through IGF receptor (IGF1R) activated the protein kinase B-mammalian target of rapamycin (AKT-mTOR) pathway, increased aerobic glycolysis, favored Th17 cell differentiation over that of Treg cells, and promoted a heightened pro-inflammatory gene expression signature. Group 3 innate lymphoid cells (ILC3s), but not ILC1s or ILC2s, were similarly responsive to IGF signaling. Mice with deficiency of IGF1R targeted to T cells failed to fully develop disease in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis. Thus, the IGF system represents a previously unappreciated pathway by which type 3 immunity is modulated and immune-mediated pathogenesis controlled.

中文翻译：

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胰岛素样生长因子是自身免疫中 T Helper 17 调节性 T 细胞平衡的关键调节剂。

辅助 T 细胞 17 (Th17) 和调节性 T (Treg) 细胞的适当平衡可维持免疫耐受和宿主防御。Th17-Treg 细胞平衡的破坏与许多免疫介导的疾病有关，其中许多疾病表现出胰岛素样生长因子 (IGF) 系统的失调。在这里，我们发现，在效应 T 细胞亚群中，Th17 和 Treg 细胞选择性表达 IGF 系统的多种成分。通过 IGF 受体 (IGF1R) 的信号传导激活了蛋白激酶 B-哺乳动物雷帕霉素靶点 (AKT-mTOR) 通路，增加了有氧糖酵解，有利于 Th17 细胞分化而不是 Treg 细胞，并促进了促炎基因表达特征的增强。第 3 组先天淋巴细胞 (ILC3) 对 IGF 信号传导有类似的反应，但 ILC1 或 ILC2 则不然。在多发性硬化症的实验性自身免疫性脑脊髓炎 (EAE) 模型中，针对 T 细胞的 IGF1R 缺陷的小鼠未能完全发展为疾病。因此，IGF 系统代表了一种以前未被认识的途径，通过该途径调节 3 型免疫并控制免疫介导的发病机制。