美国阿拉巴马大学伯明翰分校Casey T. Weaver研究团队的一项最新研究显示，自身免疫反应中胰岛素样生长因子（IGF）是辅助性T细胞17（Th17）调节T细胞平衡的关键调控因子。相关论文发表在2020年4月14日出版的《免疫》杂志上。

研究人员发现在效应T细胞亚群中，Th17和调节性T（Treg）细胞选择性表达了IGF系统的多个组分。通过IGF受体（IGF1R）传递的信号激活了蛋白激酶B、增强了有氧糖酵解；与Treg细胞相比这更有利于Th17细胞的分化，并促进促炎基因的增强表达；蛋白激酶B是哺乳动物雷帕霉素（AKT-mTOR）通路的靶点。

3型先天性淋巴样细胞（ILC3）而不是ILC1或ILC2对IGF信号有类似的响应。在多发性硬化症/实验性自身免疫性脑脊髓炎模型（EAE）中，T细胞特异性IGF1R敲出的小鼠未能完全形成该疾病。因此，IGF系统代表了以前未知的通路，通过该通路可以调节3型免疫并控制免疫介导的疾病。

据介绍，Th17和Treg细胞的平衡可维持免疫耐受和宿主的防御能力。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系统的失调。

附：英文原文

Title: Insulin-Like Growth Factors Are Key Regulators of T Helper 17 Regulatory T Cell Balance in Autoimmunity

Author: Daniel DiToro, Stacey N. Harbour, Jennifer K. Bando, Gloria Benavides, Steven Witte, Vincent A. Laufer, Carson Moseley, Jeffery R. Singer, Blake Frey, Henrietta Turner, Jens Bruning, Victor Darley-Usmar, Min Gao, Cheryl Conover, Robin D. Hatton, Stuart Frank, Marco Colonna, Casey T. Weaver

Issue&Volume: 2020/04/14

Abstract: Appropriate balance of T helper 17 (Th17) and regulatory T (Treg) cells maintainsimmune tolerance and host defense. Disruption of Th17-Treg cell balance is implicatedin a number of immune-mediated diseases, many of which display dysregulation of theinsulin-like growth factor (IGF) system. Here, we show that, among effector T cellsubsets, Th17 and Treg cells selectively expressed multiple components of the IGFsystem. Signaling through IGF receptor (IGF1R) activated the protein kinase B-mammaliantarget of rapamycin (AKT-mTOR) pathway, increased aerobic glycolysis, favored Th17cell differentiation over that of Treg cells, and promoted a heightened pro-inflammatorygene expression signature. Group 3 innate lymphoid cells (ILC3s), but not ILC1s orILC2s, were similarly responsive to IGF signaling. Mice with deficiency of IGF1R targetedto T cells failed to fully develop disease in the experimental autoimmune encephalomyelitis(EAE) model of multiple sclerosis. Thus, the IGF system represents a previously unappreciatedpathway by which type 3 immunity is modulated and immune-mediated pathogenesis controlled.

DOI: 10.1016/j.immuni.2020.03.013

Source: https://www.cell.com/immunity/fulltext/S1074-7613(20)30126-6