Cited by 312Tryptophan and brain disordersStress Responses and CortisolAdenosine and Purinergic Signaling

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

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Fan, Ke-qi, Li, Yi-yuan, Wang, Hao-li, Mao, Xin-tao, Guo, Jin-xin, Wang, Fei, Huang, Ling-jie, Li, Yi-ning +20 more·2019·Cell

Abstract

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.

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Crossref · 10.1016/j.cell.2019.10.001

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Authors
Fan, K.-Q., Li, Y.-Y., Wang, H.-L., Mao, X.-T., Guo, J.-X., Wang, F., Huang, L.-J., Li, Y.-N., Ma, X.-Y., Gao, Z.-J., Chen, W., Qian, D.-D., Xue, W.-J., Cao, Q., Zhang, L., Shen, L., Zhang, L., Tong, C., Zhong, J.-Y., Lu, W., Lu, L., Ren, K.-M., Zhong, G., Wang, Y., Tang, M., Feng, X.-H., Chai, R.-J., & Jin, J.
Affiliations
  • Zhejiang University (CN)
  • Sir Run Run Shaw Hospital (CN)
  • East China Normal University (CN)
  • Southeast University (CN)
  • ShanghaiTech University (CN)
Corresponding author
Jin, Jin
Venue
Cell
Publisher
Elsevier BV
Published
2019-10
Volume
179
Issue
4
Pages
864-879.e19
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2983084556
Cited by
312
References
62
Citations by year
2026: 30 · 2025: 43 · 2024: 57 · 2023: 45 · 2022: 54 · 2021: 41 · 2020: 39 · 2019: 3
FWCI
11.28
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Key R&D Program of China (2018YFA0800503, 2018YFD0500100)
  • Excellent Young Scientist Fund of NSFC (31822017)
  • Zhejiang Provincial Natural Science Foundation of China (LR19C080001)
  • Strategic Priority Research Program of the Chinese Academy of Science (XDA16010302)
  • National Natural Science Foundation of China (81572651, 81771675, 81622013, 81700913)
Topics
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
Keywords
stress-induced anxiety, CD4+ T cells, leukotriene B4, mitochondrial fission, purine metabolism, xanthine, adenosine A1 receptor, oligodendrocytes, amygdala, IRF1, depression, social behavior disorders, mood disorders, T cell dysfunction
MeSH terms
Amygdala, Animals, Anxiety, Behavior, Animal, Brain Diseases, Metabolic, Disease Models, Animal, Humans, Oligodendroglia, Stress, Psychological, CD4-Positive T-Lymphocytes, Xanthine, Mice, Single-Cell Analysis, Transcriptome, Mitochondrial Dynamics

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