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

First Author  Fan KQ Year  2019
Journal  Cell Volume  179
Issue  4 Pages  864-879.e19
PubMed ID  31675497 Mgi Jnum  J:339075
Mgi Id  MGI:7519272 Doi  10.1016/j.cell.2019.10.001
Citation  Fan KQ, et al. (2019) Stress-Induced Metabolic Disorder in Peripheral CD4(+) T Cells Leads to Anxiety-like Behavior. Cell 179(4):864-879.e19
abstractText  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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