Microglia drive transient insult-induced brain injury by chemotactic recruitment of CD8+ T lymphocytes

Zhongshan Shi, Pei Yu, Wei Jye Lin, Sitai Chen, Xia Hu, Siqi Chen, Jinping Cheng, Qiang Liu, Yuhua Yang, Shaojian Li, Zhan Zhang, Jiatian Xie, Jingru Jiang, Baixuan He, Yi Li, Honghong Li, Yongteng Xu, Junbo Zeng, Jialin Huang, Jinghong MeiJinhua Cai, Jiongxue Chen, Long Jun Wu, Ho Ko, Yamei Tang

Research output: Contribution to journalArticlepeer-review


The crosstalk between the nervous and immune systems has gained increasing attention for its emerging role in neurological diseases. Radiation-induced brain injury (RIBI) remains the most common medical complication of cranial radiotherapy, and its pathological mechanisms have yet to be elucidated. Here, using single-cell RNA and T cell receptor sequencing, we found infiltration and clonal expansion of CD8+ T lymphocytes in the lesioned brain tissues of RIBI patients. Furthermore, by strategies of genetic or pharmacologic interruption, we identified a chemotactic action of microglia-derived CCL2/CCL8 chemokines in mediating the infiltration of CCR2+/CCR5+ CD8+ T cells and tissue damage in RIBI mice. Such a chemotactic axis also participated in the progression of cerebral infarction in the mouse model of ischemic injury. Our findings therefore highlight the critical role of microglia in mediating the dysregulation of adaptive immune responses and reveal a potential therapeutic strategy for non-infectious brain diseases.

Original languageEnglish (US)
Pages (from-to)696-710.e9
Issue number5
StatePublished - Mar 1 2023


  • CD8 T cell
  • chemoattraction
  • ischemic stroke
  • microglia
  • radiation-induced brain injury

ASJC Scopus subject areas

  • General Neuroscience


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