Stress-Induced Metabolic Disorder in Peripheral CD4+ T Cells Leads to Anxiety-like Behavior.,Cell

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Stress-Induced Metabolic Disorder in Peripheral CD4+ T Cells Leads to Anxiety-like Behavior.
Cell ( IF 45.5 ) Pub Date : 2019-10-31 , DOI: 10.1016/j.cell.2019.10.001
Ke-Qi Fan ₁ , Yi-Yuan Li ₁ , Hao-Li Wang ₁ , Xin-Tao Mao ₁ , Jin-Xin Guo ₁ , Fei Wang ₁ , Ling-Jie Huang ₂ , Yi-Ning Li ₁ , Xiang-Yu Ma ₃ , Zheng-Jun Gao ₁ , Wei Chen ₄ , Dan-Dan Qian ₅ , Wen-Jin Xue ₅ , Qian Cao ₂ , Lei Zhang ₂ , Li Shen ₁ , Long Zhang ₁ , Chao Tong ₁ , Jiang-Yan Zhong ₁ , Wei Lu ₅ , Ling Lu ₆ , Ke-Ming Ren ₂ , Guisheng Zhong ₇ , Yuan Wang ₄ , Mingliang Tang ₅ , Xin-Hua Feng ₁ , Ren-Jie Chai ₃ , Jin Jin ₈

Affiliation

MOE Laboratory of Biosystem Homeostasis and Protection and Life Sciences Institute, Zhejiang University, Hangzhou 310058, China.
Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou 310016, China.
Key Laboratory for Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing 210096, China; Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China; Institute for Stem Cell and Regeneration, Chinese Academy of Science, Beijing, China.
Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China.
Key Laboratory for Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing 210096, China.
Department of Otolaryngology Head and Neck Surgery, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, 210008, Jiangsu, China.
iHuman Institute, ShanghaiTech University, Shanghai 201210, China.
MOE Laboratory of Biosystem Homeostasis and Protection and Life Sciences Institute, Zhejiang University, Hangzhou 310058, China; Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou 310016, China.

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.

中文翻译：

应激诱导的外周CD4 + T细胞代谢紊乱导致焦虑样行为。

身体或精神上的压力会导致大脑神经可塑性，并增加患抑郁症和焦虑症的风险。压力暴露引起外周T淋巴细胞功能障碍。然而，尚未充分建立在情绪障碍中外周T淋巴细胞的病理学作用和潜在的调节机制。在这里，我们表明缺乏CD4 + T细胞可以保护小鼠免受应激诱导的焦虑样行为。物理压力诱导的白三烯B4触发CD4 + T细胞中的严重线粒体裂变，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。线粒体裂变通过CD4 + T细胞中干扰素调节因子1的积累促进嘌呤从头合成。我们的研究暗示了CD4 + T细胞中的嘌呤代谢紊乱与压力驱动的焦虑样行为之间的关键联系。

更新日期：2019-11-09

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