Stress-Induced Metabolic Disorder in Peripheral CD4+ T Cells Leads to Anxiety-like Behavior
Stress-Induced Metabolic Disorder in Peripheral CD4+ T Cells Leads to Anxiety-like Behavior
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压力诱导的外周 CD4( ) T 细胞代谢紊乱导致焦虑样行为
DOI：
10.1016/j.cell.2019.10.001
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发表时间：
2019-10-31
期刊：
影响因子：
64.5
通讯作者：
Jin, Jin
中科院分区：
文献类型：
--
作者：
Fan, Ke-qi;Li, Yi-yuan;Jin, Jin
身体或精神压力会导致大脑的神经可塑性，增加抑郁和焦虑的风险。应激暴露导致外周血T淋巴细胞功能障碍。然而，外周血T淋巴细胞在心境障碍中的病理作用和潜在的调节机制尚未得到很好的建立。在这里，我们表明，缺乏CD4（+）T细胞保护小鼠免受应激诱导的焦虑样行为。身体应激诱导的白三烯B4触发CD4（+）T细胞中严重的线粒体分裂，这进一步导致各种行为异常，包括焦虑、抑郁和社交障碍。代谢组学和单细胞转录组显示，CD4（+）T细胞衍生的黄嘌呤通过腺苷受体A1作用于左杏仁核中的少突胶质细胞。线粒体分裂通过干扰素调节因子1在CD4（+）T细胞中的积累促进嘌呤的从头合成我们的研究暗示了CD4（+）T细胞中嘌呤代谢紊乱与压力驱动的焦虑样行为之间的关键联系。
Physical or mental stress leads to neuroplasticity in the brain and increases the risk of depression and anxiety. Stress exposure causes the dysfunction of peripheral T lymphocytes. However, the pathological role and underlying regulatory mechanism of peripheral T lymphocytes in mood disorders have not been well established. Here, we show that the lack of CD4(+) T cells protects mice from stress-induced anxiety-like behavior. Physical stress-induced leukotriene B4 triggers severe mitochondrial fission in CD4(+) T cells, which further leads to a variety of behavioral abnormalities including anxiety, depression, and social disorders. Metabolomic profiles and single-cell transcriptome reveal that CD4(+) T cell-derived xanthine acts on oligodendrocytes in the left amygdala via adenosine receptor A1. Mitochondrial fission promotes the de novo synthesis of purine via interferon regulatory factor 1 accumulation in CD4(+) T cells. Our study implicates a critical link between a purine metabolic disorder in CD4(+) T cells and stress-driven anxiety-like behavior.