BST2 expression at astrocyte borders promotes microglial recruitment via the C3/C3aR signaling
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.
Authors
- Mengqi Yuan (ORCID: https://orcid.org/0000-0002-6933-7416)
- Ying He (ORCID: https://orcid.org/0009-0008-9705-7690)
- Bingqiao Wang
- Xiaofeng Cheng (ORCID: https://orcid.org/0000-0002-7079-7612)
- Feng Mei (ORCID: https://orcid.org/0000-0003-4125-1570)
- Wenjie Zi (ORCID: https://orcid.org/0000-0001-6323-2659)
- Zhao Yuan (ORCID: https://orcid.org/0000-0001-6410-0711)
- Hongting Zheng (ORCID: https://orcid.org/0000-0002-6930-0103)
- Hui Lü (ORCID: https://orcid.org/0000-0003-1640-239X)
- Chenhao Zhao
- Qingwu Yang
- Liuyongwei Wang
- Chengkang He
- Yiliang Fang (ORCID: https://orcid.org/0000-0003-2414-2532)
- Sen Lin (ORCID: https://orcid.org/0000-0001-9346-8187)
- Jianqin Niu (ORCID: https://orcid.org/0000-0003-0642-7542)
- Shuang Zhang (ORCID: https://orcid.org/0009-0001-6489-968X)
- Bao‐liang Sun (ORCID: https://orcid.org/0000-0002-5178-1754)
- Jinchuan Zhou (ORCID: https://orcid.org/0000-0001-5716-5170)
- Qi Xie (ORCID: https://orcid.org/0000-0003-2177-7348)
- Linlin Hu (ORCID: https://orcid.org/0000-0001-6213-8732)
- Xiaoman Wang (ORCID: https://orcid.org/0000-0002-6009-2619)
- Qian He
- Chang‐Xiong Gong
Institutions
- Army Medical University (CN)
- Dalian Medical University (CN)
- Daping Hospital (CN)
- Second Affiliated Hospital of Chongqing Medical University (CN)
- Shandong First Medical University (CN)
- Chongqing Medical University (CN)
Publication Details
- Journal
- Neuron
- Published
- 2025-10-24
- DOI
- https://doi.org/10.1016/j.neuron.2025.09.038
- Citations
- 1
- Primary Topic
- Neuroinflammation and Neurodegeneration Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 0.84