Insulin Receptor-Mediated Stimulation Boosts T Cell Immunity during Inflammation and Infection
Insulin Receptor-Mediated Stimulation Boosts T Cell Immunity during Inflammation and Infection
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DOI：
10.1016/j.cmet.2018.08.003
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发表时间：
2018-12-04
期刊：
影响因子：
29
通讯作者：
Winer, Daniel A.
中科院分区：
文献类型：
--
作者：
Tsai, Sue;Clemente-Casares, Xavier;Winer, Daniel A.
T细胞代表细胞介导的免疫的关键效应子。活化的T细胞在效应分化期间参与代谢重编程以适应能量需求的动态变化。在这里，我们表明，激素，胰岛素和下游信号通过其胰岛素受体形状适应性免疫功能，通过调节T细胞代谢。缺乏胰岛素受体表达的T细胞（LckCre+ insr（fl/fl））显示降低的抗原特异性增殖和促炎细胞因子的受损产生。在体内，T细胞特异性胰岛素受体缺陷减少T细胞驱动的结肠炎症。在A/PR 8（H1N1）严重流感感染的模型中，T细胞上胰岛素受体的缺乏减少了对流感病毒抗原的抗原特异性免疫。从机制上讲，胰岛素受体信号传导加强了支持T细胞营养摄取和相关糖酵解和呼吸能力的代谢程序。这些数据突出了胰岛素受体信号传导作为整合免疫代谢途径的重要节点，以驱动健康和疾病中的最佳T细胞效应子功能。
T cells represent a critical effector of cell-mediated immunity. Activated T cells engage in metabolic reprogramming during effector differentiation to accommodate dynamic changes in energy demands. Here, we show that the hormone, insulin, and downstream signaling through its insulin receptor shape adaptive immune function through modulating T cell metabolism. T cells lacking insulin receptor expression (LckCre+ insr(fl/fl)) show reduced antigen-specific proliferation and compromised production of pro-inflammatory cytokines. In vivo, T cell-specific insulin receptor deficiency reduces T cell-driven colonic inflammation. In a model of severe influenza infection with A/PR8 (H1N1), lack of insulin receptor on T cells curtails antigen-specific immunity to influenza viral antigens. Mechanistically, insulin receptor signaling reinforces a metabolic program that supports T cell nutrient uptake and associated glycolytic and respiratory capacities. These data highlight insulin receptor signaling as an important node integrating immunometabolic pathways to drive optimal T cell effector function in health and disease.