Stress-Induced Metabolic Disorder in Peripheral CD4(+) T Cells Leads to Anxiety-like Behavior
Fan, Ke-qi1,2; Li, Yi-yuan1,2; Wang, Hao-li1,2; Mao, Xin-tao1,2; Guo, Jin-xin1,2; Wang, Fei1,2; Huang, Ling-jie3; Li, Yi-ning1,2; Ma, Xiang-yu4,5,6; Gao, Zheng-jun1,2; Chen, Wei7,8; Qian, Dan-dan4; Xue, Wen-jin4; Cao, Qian3; Zhang, Lei3; Shen, Li1,2; Zhang, Long1,2; Tong, Chao1,2; Zhong, Jiang-yan1,2; Lu, Wei4; Lu, Ling9; Ren, Ke-ming3; Zhong, Guisheng10; Wang, Yuan7,8; Tang, Mingliang4; Feng, Xin-hua1,2; Chai, Ren-jie4,5,6; Jin, Jin1,2,3
2019-10-31
Source PublicationCELL
ISSN0092-8674
Volume179Issue:4Pages:864-+
Status已发表
DOI10.1016/j.cell.2019.10.001
AbstractPhysical 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.
Indexed BySCI
Language英语
Funding ProjectNational 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 Research AreaBiochemistry & Molecular Biology ; Cell Biology
WOS SubjectBiochemistry & Molecular Biology ; Cell Biology
WOS IDWOS:000493898000007
PublisherCELL PRESS
EISSN1097-4172
WOS KeywordMITOCHONDRIAL DYNAMICS ; MICE ; AMYGDALA ; ACTIVATION ; DEPRESSION ; BRAIN ; FEAR ; DEFICIENCY ; MECHANISMS ; INHIBITORS
Original Document TypeArticle
Citation statistics
Cited Times:11[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://kms.shanghaitech.edu.cn/handle/2MSLDSTB/102232
CollectioniHuman研究所_PI研究组_钟桂生组
Corresponding AuthorChai, Ren-jie; Jin, Jin
Affiliation1.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
Recommended Citation
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-+.
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