Neural Regeneration Research ›› 2026, Vol. 21 ›› Issue (3): 855-868.doi: 10.4103/NRR.NRR-D-24-00986

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Roles of central nervous system resident and recruited macrophages in the brain barrier system

Ze Liu1, #, Teng Cheng1, #, Hongtian Dong1, #, Dingya Sun1 , Yan Wang2 , Jiayan Li3 , Zhongwang Yu1, *, Li Cao1, *   

  1. 1 Institute of Neuroscience Key Laboratory of Molecular Neurobiology of Ministry of Education and the Collaborative Innovation Center for Brain Science SMMU, Shanghai, China;  2 Department of Pharmacy, Shanghai Baoshan District Wusong Central Hospital (Zhongshan Hospital Wusong Branch, Fudan University), Shanghai, China;  3 Neurovascular Center, Changhai Hospital SMMU, Shanghai, China
  • Online:2026-03-15 Published:2025-07-01
  • Contact: Li Cao, PhD, caoli@smmu.edu.cn; Zhongwang Yu, PhD, yzwqqq@smmu.edu.cn.
  • Supported by:
    This work was supported by Ministry of Science and Technology China Brain Initiative Grant, No. 2022ZD0204702 (to ZY); the National Natural Science Foundation of China, No. 82371357 (to LC); Foundation for Military Medicine, No. 16QNP085 (to ZY); Navy Medical University Basic Medical College “Yi Zhang” Basic Medical Talent Development and Support Program, Nos. JCYZRC-D-022 (to TC) and JCYZRC-D-024 (to HD); and Science and Technology Innovation Special Fund of Shanghai Baoshan District, No. 2023-E-05 (to YW).

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Abstract: Macrophages in the brain barrier system include microglia in the brain parenchyma, border-associated macrophages at the brain’s borders, and recruited macrophages. They are responsible for neural development, maintenance of homeostasis, and orchestrating immune responses. With the rapid exploitation and development of new technologies, there is a deeper understanding of macrophages in the brain barrier system. Here we review the origin, development, important molecules, and functions of macrophages, mainly focusing on microglia and border-associated macrophages. We also highlight some advances in single-cell sequencing and significant cell markers. We anticipate that more advanced methods will emerge to study resident and recruited macrophages in the future, opening new horizons for neuroimmunology and related peripheral immune fields.

Key words: border-associated macrophages, brain barrier system, cell markers, development, microglia, neuroimmunology, recruited macrophages, resident macrophages, single-cell sequencing