近日，浙江大学靳津课题组和东南大学柴人杰课题组合作发现，应激引起的外周CD4⁺T细胞代谢紊乱能够导致焦虑样行为。2019年10月31日，国际学术期刊《细胞》发表了该研究成果。

研究人员发现，CD4⁺T细胞的缺乏能够保护小鼠免受应激引起的焦虑样行为。物理应激引起的白三烯B4触发CD4⁺T细胞中的严重线粒体分裂，进而导致各种行为异常，包括焦虑、抑郁和社交障碍。代谢组学特征和单细胞转录组显示，CD4⁺T细胞来源的黄嘌呤通过腺苷受体A1作用于左杏仁核的少突胶质细胞。线粒体分裂通过CD4⁺T细胞中干扰素调节因子1的积累促进嘌呤从头合成。这项研究提示了CD4⁺T细胞中嘌呤代谢紊乱与压力引起的焦虑样行为之间的关键联系。

据介绍，身体或精神紧张会导致大脑神经可塑性并增加抑郁症和焦虑症的风险。应激暴露导致外周T淋巴细胞功能障碍。然而，目前的研究尚未充分建立在情绪障碍中外周T淋巴细胞的病理作用和潜在的调节机制。

附：英文原文

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.