@article{f89e83da10884afa927bea71342a7072,
title = "Microglia drive transient insult-induced brain injury by chemotactic recruitment of CD8+ T lymphocytes",
abstract = "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.",
keywords = "CD8 T cell, chemoattraction, ischemic stroke, microglia, radiation-induced brain injury",
author = "Zhongshan Shi and Pei Yu and Lin, {Wei Jye} and Sitai Chen and Xia Hu and Siqi Chen and Jinping Cheng and Qiang Liu and Yuhua Yang and Shaojian Li and Zhan Zhang and Jiatian Xie and Jingru Jiang and Baixuan He and Yi Li and Honghong Li and Yongteng Xu and Junbo Zeng and Jialin Huang and Jinghong Mei and Jinhua Cai and Jiongxue Chen and Wu, {Long Jun} and Ho Ko and Yamei Tang",
note = "Funding Information: This study was supported by the National Natural Science Foundation of China (no. 81925031 and 81820108026) and Guangzhou Science and Technology Program Key Projects (202007030001) to Y.T.; National Natural Science Foundation of China (no. 82103775) to Z.S.; National Natural Science Foundation of China (no. 81972967), Guangdong Science and Technology Department (no. 2020B1212060018 and 2020B1212030004), and Guangdong Basic and Applied Basic Research Foundation (2019A1515011754) to W.-J.L.; National Natural Science Foundation of China (no. 81872549) and Science and Technology Planning Project of Guangzhou (201704030033) to Y.L.; National Natural Science Foundation of China (no. 82003389) to H.L.; Youth Program of National Natural Science Foundation of China (no. 81801229) to Y.X.; China Postdoctoral Science Foundation (2020M672993) to Q.L.; China Postdoctoral Science Foundation (2020TQ0374, 2020M683095) to J. Cheng; and the China Postdoctoral Science Foundation (2021M693635) to B.H. We thank Dr. Lin Wang from the Department of Pathology, Sun Yat-sen Memorial Hospital, for her professional examination of the pathological specimens. We also thank Prof. Xiang Yu for critically reading the manuscript. Conceptualization, Y.T. Z.S. P.Y. and W.-J.L.; methodology, Siqi Chen, J. Cheng, Q.L. Y.Y. S.L. Z.Z. J.X. J.J. B.H. L.-J.W. and H.K.; validation, X.H. Siqi Chen, and Z.Z.; investigation, Z.S. Y.L. H.L. Y.X. J.Z. J.H. and J.M.; writing – original draft, Z.S. P.Y. W.-J.L. Sitai Chen, and X.H.; writing – review & editing, Y.T. W.-J.L. L.-J.W. and H.K.; visualization, Sitai Chen, J. Cai, and J. Chen; supervision, Y.T. and W.-J.L.; project administration, Y.T.; funding acquisition, Y.T. Z.S. W.-J.L. Y.L. H.L. Y.X. Q.L. J. Cheng, and B.H. The authors declare no competing interests. Funding Information: This study was supported by the National Natural Science Foundation of China (no. 81925031 and 81820108026 ) and Guangzhou Science and Technology Program Key Projects ( 202007030001 ) to Y.T.; National Natural Science Foundation of China (no. 82103775 ) to Z.S.; National Natural Science Foundation of China (no. 81972967 ), Guangdong Science and Technology Department (no. 2020B1212060018 and 2020B1212030004 ), and Guangdong Basic and Applied Basic Research Foundation ( 2019A1515011754 ) to W.-J.L.; National Natural Science Foundation of China (no. 81872549 ) and Science and Technology Planning Project of Guangzhou ( 201704030033 ) to Y.L.; National Natural Science Foundation of China (no. 82003389 ) to H.L.; Youth Program of National Natural Science Foundation of China (no. 81801229 ) to Y.X.; China Postdoctoral Science Foundation ( 2020M672993 ) to Q.L.; China Postdoctoral Science Foundation ( 2020TQ0374 , 2020M683095 ) to J. Cheng; and the China Postdoctoral Science Foundation ( 2021M693635 ) to B.H. We thank Dr. Lin Wang from the Department of Pathology, Sun Yat-sen Memorial Hospital, for her professional examination of the pathological specimens. We also thank Prof. Xiang Yu for critically reading the manuscript. Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",
year = "2023",
month = mar,
day = "1",
doi = "10.1016/j.neuron.2022.12.009",
language = "English (US)",
volume = "111",
pages = "696--710.e9",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "5",
}