作者
Ke-qi Fan,Yi-yuan Li,Haoli Wang,Xin-tao Mao,Jin-xin Guo,Fei Wang,Liying Huang,Yining Li,Xiangyu Ma,Zijun Gao,Wei Chen,Dandan Qian,Wen-jin Xue,Qian Cao,Lei Zhang,Li Shen,Long Zhang,Chao Tong,Jiang-yan Zhong,Wei Lü,Ling Lü,Ke-ming Ren,Guisheng Zhong,Yuan Wang,Mingliang Tang,Xin‐Hua Feng,Renjie Chai,Jin Jin
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.