1. Academic Validation
  2. BST2 expression at astrocyte borders promotes microglial recruitment via the C3/C3aR signaling

BST2 expression at astrocyte borders promotes microglial recruitment via the C3/C3aR signaling

  • Neuron. 2025 Oct 24:S0896-6273(25)00751-2. doi: 10.1016/j.neuron.2025.09.038.
Shuang Zhang 1 Mengqi Yuan 1 Jin Zhou 2 Yuan Zhao 1 Liuyongwei Wang 3 Changxiong Gong 1 Hui Lu 1 Xiaofeng Cheng 1 Xiaoman Wang 1 Qian He 1 Linlin Hu 1 Bingqiao Wang 1 Chengkang He 1 Yiliang Fang 1 Sen Lin 1 Wenjie Zi 4 Ying He 3 Chenhao Zhao 1 Hongting Zheng 5 Jianqin Niu 6 Feng Mei 6 Baoliang Sun 7 Qi Xie 8 Qingwu Yang 9
Affiliations

Affiliations

  • 1 Department of Neurology, Second Affiliated Hospital, Army Medical University (Third Military Medical University), State Key Laboratory of Trauma and Chemical Poisoning, Chongqing 400037, China; Chongqing Institute for Brain and Intelligence, CIBI, Chongqing 401336, China.
  • 2 Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing, China.
  • 3 Department of Neurology, Second Affiliated Hospital, Army Medical University (Third Military Medical University), State Key Laboratory of Trauma and Chemical Poisoning, Chongqing 400037, China; Department of Medical Psychology, Neurological Medical Center, Second Affiliated Hospital, Army Medical University, Chongqing 400037, China.
  • 4 Department of Neurology, Second Affiliated Hospital, Army Medical University (Third Military Medical University), State Key Laboratory of Trauma and Chemical Poisoning, Chongqing 400037, China.
  • 5 Department of Endocrinology, Translational Research of Diabetes Key Laboratory of Chongqing Education Commission of China, the Second Affiliated Hospital of Army Medical University, Chongqing 400037, China.
  • 6 Department of Histology and Embryology, Chongqing Key Laboratory of Neurobiology, Brain and Intelligence Research Key Laboratory of Chongqing Education Commission, Third Military Medical University, Chongqing, China.
  • 7 Department of Neurology, The Second Affiliated Hospital, Key Laboratory of Cerebral Microcirculation in Universities of Shandong, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian 271000, Shandong, China.
  • 8 Department of Neurology, Second Affiliated Hospital, Army Medical University (Third Military Medical University), State Key Laboratory of Trauma and Chemical Poisoning, Chongqing 400037, China; Chongqing Institute for Brain and Intelligence, CIBI, Chongqing 401336, China. Electronic address: xieqi@tmmu.edu.cn.
  • 9 Department of Neurology, Second Affiliated Hospital, Army Medical University (Third Military Medical University), State Key Laboratory of Trauma and Chemical Poisoning, Chongqing 400037, China; Chongqing Institute for Brain and Intelligence, CIBI, Chongqing 401336, China. Electronic address: yangqwmlys@tmmu.edu.cn.
Abstract

Following central nervous system injury, astrocytes form borders that were traditionally regarded as physical barriers. Emerging evidence demonstrates their capacity to regulate inflammation and repair; however, the specific characteristics of these border astrocytes and their interactions with immune cells remain insufficiently characterized. Using single-cell Sequencing and spatial transcriptomics, we identified astrocytes expressing the interferon-inducible protein bone marrow stromal cell antigen 2 (BST2) enriched at injury boundaries that promote microglial recruitment via C3/C3aR signaling. Astrocyte-specific Bst2 knockout reduced astrocyte-microglia interactions and attenuated border formation, correlating with early neurological improvement after stroke. Mechanistically, BST2 enhanced C3 expression through protein kinase C-βII (PKCβII) phosphorylation. Moreover, treatment with a BST2 monoclonal antibody diminished astrocyte-microglia interactions and improved neurological function. Together, these findings highlight the pivotal role of astrocyte-microglia interactions in lesion border formation and suggest that BST2 may represent a therapeutic target to modulate these interactions and reduce early brain injury after stroke.

Keywords

astrocyte borders; astrocyte-microglia interactions; ischemic stroke; neuroinflammation.

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