中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (10): 4538-4549.doi: 10.4103/NRR.NRR-D-25-00868

• 综述:神经损伤修复保护与再生 • 上一篇    下一篇

CD11c+小胶质细胞：从基础研究到临床应用

  

  • 出版日期:2026-10-15 发布日期:2026-06-11
  • 基金资助:
    北京市自然科学基金（7244410，L248070），国家自然科学基金（82402786，82272478），辽宁省科学技术厅博士创业项目（2023-BSBA-148），中国博士后科学基金博士后研究资助项目（GZC20242291），中国博士后科学基金（2025M774434）

CD11c+ microglia: From basic research to clinical application

Zipeng Zhou1, #, Yongfei Zhao1, #, Xiangyi Fan2, #, Jinhui Zhang1, Ruihan Niu1, Yifei Ma1, Fei Xie1, Peifu Tang1, Xifan Mei3, *, Licheng Zhang1, *, Junhao Deng1, 4, *   

  1. 1Department of Orthopedics, Senior Department of Orthopedics, Chinese PLA Hospital, Beijing, China; 
    2Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning Province, China; 
    3Liaoning Vocational College of Medicine, Shenyang, Liaoning Province, China; 
    4School of Life Science, Tsinghua University, Beijing, China
  • Online:2026-10-15 Published:2026-06-11
  • Contact: Junhao Deng, MD, deng_junh@163.com; Licheng Zhang, MD, zhanglcheng218@126.com; Xifan Mei, MD, meixifan1971@163.com.
  • Supported by:
    This work was supported by the Natural Science Foundation of Beijing, Nos. 7244410, L248070 (both to JD); the National Natural Science Foundation of China, Nos. 82402786 (to JD), 82272478 (to PT); Liaoning Provincial Department of Science and Technology Doctoral Startup Project, No. 2023-BSBA-148 (to ZZ); Postdoctoral Fellowship Program of CPSF, No. GZC20242291 (to ZZ); China Postdoctoral Science Foundation, No. 2025M774434 (to ZZ).

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摘要：

CD11c+小胶质细胞是功能特化的亚群，在多种中枢神经系统疾病的病理生理过程中发挥关键作用。文章述整合了有力证据，表明CD11c+小胶质细胞具有独特的转录组和表观遗传特征，这些特性使其区别于稳态小胶质细胞，并支撑其特化功能。在发育过程中，这类细胞对少突胶质细胞成熟及白质完整性至关重要，尤其在胼胝体和小脑等区域。在神经退行性疾病（如阿尔茨海默病、肌萎缩侧索硬化症）及中枢神经系统损伤（如脑卒中、脊髓损伤）的临床前模型中，它们始终呈现神经保护表型。这些细胞在淀粉样斑块及受损神经元附近展现增强的吞噬能力，协助清除病理性蛋白质聚集物和细胞碎片，从而减轻神经毒性并促进修复环境形成。当前研究认为，特定微环境信号（尤其是危险相关分子模式DAMPs和细胞因子如干扰素γ）是驱动CD11c+小胶质细胞分化活化的核心机制，其中TREM2-APOE信号轴作为调控其存活、增殖及功能状态的关键通路已获广泛认可。CD11c+小胶质细胞的可塑性受CSF1R、SIRPα-CD47、干扰素γ及补体级联等多重信号通路调控。新兴治疗策略旨在通过基因靶向、代谢干预及免疫调节手段调控其活性，具体途径包括TREM2激动剂、CSF1R抑制剂或纳米药物递送技术。然而在明确CD11c+特异性生物标志物、解析环境依赖性功能及实现靶向递送方面仍存挑战。未来发展需清晰解决个体发育问题，破译调控其表型可塑性的分子开关，并开发高度特异性治疗策略以发挥其有益功能，从而为神经系统疾病开辟新型干预途径。


https://orcid.org/0000-0002-9596-1861 (Junhao Deng); 

https://orcid.org/0000-0002-2841-1851 (Licheng Zhang); 

https://orcid.org/0000-0003-3698-0525 (Xifan Mei)

关键词: CD11c+小胶质细胞, 疾病相关小胶质细胞, 小胶质细胞亚群, 髓鞘形成, 神经系统疾病, 神经炎症, 神经免疫学, 神经退行性变, 吞噬作用

Abstract: CD11c+ microglia are a functionally specialized subpopulation of microglia that play a crucial role in the pathophysiological processes of various central nervous system diseases. This review synthesizes compelling evidence that CD11c+ microglia exhibit unique transcriptomic and phagocytic characteristics. These characteristics distinguish them from homeostatic microglia and support their specialized functions. During development, CD11c+ microglia are crucial for the maturation of oligodendrocytes and the integrity of white matter, particularly in regions such as the corpus callosum and cerebellum. In preclinical models of neurodegenerative diseases (such as Alzheimer’s disease and amyotrophic lateral sclerosis) and central nervous system injuries (such as stroke and spinal cord injury), they are consistently associated with neuroprotective phenotypes. CD11c+ microglia exhibit enhanced phagocytic capacity near amyloid plaques and damaged neurons, helping to clear pathological protein aggregates and cell debris, thereby reducing neurotoxicity and promoting a repair environment. The current consensus is that specific microenvironmental cues, particularly hazard signaling molecules damage-associated molecular patterns and cytokines (such as interferon-γ), are the main drivers of the differentiation and activation of CD11c+ microglia. Among these, the TREM2-APOE signaling axis is a key and widely accepted regulatory pathway for their survival, proliferation, and functional status. The plasticity of CD11c+ microglia is regulated by multiple signaling pathways, including CSF1R, SIRPα-CD47, interferon-γ, and the complement cascade. Emerging therapeutic strategies aim to regulate their activities through gene targeting, metabolic intervention, and immune regulation using TREM2 agonists, CSF1R inhibitors, or nanopharmacological methods. However, challenges remain in defining specific CD11c+ biomarkers, understanding environment-dependent functions, and achieving targeted delivery. Future prospects depend on clearly addressing individual developmental issues, deciphering the molecular switches that control phenotypic plasticity, and developing highly specific therapeutic strategies to leverage their beneficial functions, thereby paving the way for new intervention methods for neurological diseases. 

Key words: CD11c+ microglia, disease-associated microglia, microglial subsets, myelination, neurodegeneration, neuroimmunology, neuroinflammation, neurological diseases