Stress-Induced Metabolic Disorder in Peripheral CD4(+) T Cells Leads to Anxiety-like Behavior

doi:10.1016/j.cell.2019.10.001

	Stress-Induced Metabolic Disorder in Peripheral CD4(+) T Cells Leads to Anxiety-like Behavior
	Fan, Ke-qi 1,2; Li, Yi-yuan 1,2; Wang, Hao-li 1,2; Mao, Xin-tao 1,2; Guo, Jin-xin 1,2; Wang, Fei 1,2; Huang, Ling-jie 3; Li, Yi-ning 1,2; Ma, Xiang-yu 4,5,6; Gao, Zheng-jun 1,2; Chen, Wei 7,8; Qian, Dan-dan 4; Xue, Wen-jin 4; Cao, Qian 3; Zhang, Lei 3; Shen, Li 1,2; Zhang, Long 1,2; Tong, Chao 1,2; Zhong, Jiang-yan 1,2; Lu, Wei 4; Lu, Ling 9; Ren, Ke-ming 3; Zhong, Guisheng10 ; Wang, Yuan 7,8; Tang, Mingliang 4; Feng, Xin-hua 1,2; Chai, Ren-jie 4,5,6; Jin, Jin 1,2,3
	2019-10-31
发表期刊	CELL
ISSN	0092-8674
EISSN	1097-4172
卷号	179 期号:4 页码:864-+
发表状态	已发表
DOI	10.1016/j.cell.2019.10.001
摘要	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.
收录类别	SCI ; SCIE
语种	英语
资助项目	National Natural Science Foundation of China[81572651] ; National Natural Science Foundation of China[81771675] ; National Natural Science Foundation of China[81622013] ; National Natural Science Foundation of China[81700913]
WOS研究方向	Biochemistry & Molecular Biology ; Cell Biology
WOS类目	Biochemistry & Molecular Biology ; Cell Biology
WOS记录号	WOS:000493898000007
出版者	CELL PRESS
WOS关键词	MITOCHONDRIAL DYNAMICS ; MICE ; AMYGDALA ; ACTIVATION ; DEPRESSION ; BRAIN ; FEAR ; DEFICIENCY ; MECHANISMS ; INHIBITORS
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/102232
专题	iHuman研究所_PI研究组_钟桂生组
通讯作者	Chai, Ren-jie; Jin, Jin
作者单位	1.Zhejiang Univ, MOE Lab Biosyst Homeostasis & Protect, Hangzhou 310058, Zhejiang, Peoples R China 2.Zhejiang Univ, Life Sci Inst, Hangzhou 310058, Zhejiang, Peoples R China 3.Zhejiang Univ, Coll Med, Sir Run Run Shaw Hosp, Hangzhou 310016, Zhejiang, Peoples R China 4.Southeast Univ, Jiangsu Prov High Tech Key Lab Biomed Res, Inst Life Sci, Key Lab Dev Genes & Human Dis,Minist Educ, Nanjing 210096, Jiangsu, Peoples R China 5.Nantong Univ, Coinnovat Ctr Neuroregenerat, Nantong 226001, Peoples R China 6.Chinese Acad Sci, Inst Stem Cell & Regenerat, Beijing, Peoples R China 7.East China Normal Univ, Inst Biomed Sci, Shanghai Key Lab Regulatory Biol, 500 Dongchuan Rd, Shanghai 200241, Peoples R China 8.East China Normal Univ, Sch Life Sci, 500 Dongchuan Rd, Shanghai 200241, Peoples R China 9.Nanjing Univ, Med Sch, Nanjing Drum Tower Hosp, Dept Otolaryngol Head & Neck Surg, Nanjing 210008, Jiangsu, Peoples R China 10.ShanghaiTech Univ, iHuman Inst, Shanghai 201210, Peoples R China
推荐引用方式 GB/T 7714	Fan, Ke-qi,Li, Yi-yuan,Wang, Hao-li,et al. Stress-Induced Metabolic Disorder in Peripheral CD4(+) T Cells Leads to Anxiety-like Behavior[J]. CELL,2019,179(4):864-+.
APA	Fan, Ke-qi.,Li, Yi-yuan.,Wang, Hao-li.,Mao, Xin-tao.,Guo, Jin-xin.,...&Jin, Jin.(2019).Stress-Induced Metabolic Disorder in Peripheral CD4(+) T Cells Leads to Anxiety-like Behavior.CELL,179(4),864-+.
MLA	Fan, Ke-qi,et al."Stress-Induced Metabolic Disorder in Peripheral CD4(+) T Cells Leads to Anxiety-like Behavior".CELL 179.4(2019):864-+.