中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2025, Vol. 20 ›› Issue (5): 1277-1292.doi: 10.4103/NRR.NRR-D-23-01385

• 综述:脑损伤修复保护与再生 • 上一篇    下一篇

缺血性脑卒中免疫炎症过程中T细胞与小胶质细胞的互作

  

  • 出版日期:2025-05-15 发布日期:2024-10-29

T cell interactions with microglia in immuneinflammatory processes of ischemic stroke

Yuxiao Zheng1, # , Zilin Ren1, # , Ying Liu1, # , Juntang Yan2 , Congai Chen3 , Yanhui He1 , Yuyu Shi 1 , Fafeng Cheng1 , Qingguo Wang1, * , Changxiang Li 1, * , Xueqian Wang1, *   

  1. 1 School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China; 

    2 Library, Beijing University of Chinese Medicine, Beijing, China; 

    3 Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China

  • Online:2025-05-15 Published:2024-10-29
  • Contact: Qingguo Wang, PhD, wangqg8558@sina.com; Changxiang Li, PhD, changxiang1202@163.com; Xueqian Wang, PhD, wxqbucm@126.com
  • Supported by:
    This work was supported by the Nattonal Natural Science Foundatton of China, Nos. 82104560 (to CL), U21A20400 (to QW); the Natural Science Foundatton of Beijing, No. 7232279 (to XW); the Project of Beijing University of Chinese Medicine, No. 2022-JYB-JBZR-004 (to XW).

PDF

101

摘要：

脑缺血后继发性损伤的机制可能是由于缺血性脑卒中后产生脑部炎症，促进神经元死亡，抑制神经组织再生。小胶质细胞作为缺血性脑卒中后最先被激活的免疫细胞，在急性缺血性脑卒中的进展过程中发挥着重要的免疫调节作用。缺血性脑卒中发生后，外周血免疫细胞(主要是T细胞)会被脑部免疫细胞分泌的趋化因子招募到中枢神经系统，与中枢细胞(主要是小胶质细胞)相互作用，引发继发性神经免疫反应。这篇综述阐述了缺血性那卒中免疫炎症过程中T细胞与小胶质细胞的相互作用。①在缺血性脑卒中中，T细胞和小胶质细胞表现出更明显的协同作用，表现在Th1、Th17和M1小胶质细胞可共同分泌干扰素γ、肿瘤坏死因子α和白细胞介素1β等促炎因子，促进神经炎症，加重脑损伤;Th2、Treg和M2小胶质细胞可共同分泌白细胞介素4、白细胞介素10和转化生长因子β等抗炎因子，抑制神经炎症的发展，并分泌脑源性神经营养因子等生长因子，促进神经再生，修复脑损伤。②小胶质细胞和T细胞之间的免疫相互作用会影响神经炎症的后续发展方向，进而决定缺血性脑卒中的预后。③目前已有临床试验通过使用免疫抑制剂芬戈莫德 (fingolimod)或过量使用Treg细胞来调节T细胞与小胶质细胞之间的相互作用，使其向抗炎方向发展，从而促进神经组织修复，减轻缺血性脑卒中造成的神经损伤，但目前此类临床研究证据还比较少。④T细胞亚群和活化的小胶质细胞主要通过分泌炎症因子协同调控缺血性脑卒中的炎症进展。未来，缺血性脑卒中治疗的重点研究方向可以从这里入手，通过促进Th2和Treg细胞的生成以及M2型小胶质细胞的活化来增强抗炎因子的分泌，从而缓解神经炎症，促进神经组织的修复。

https://orcid.org/0000-0002-7682-3877 (Xueqian Wang); https://orcid.org/0000-0001-8382-1717 (Changxiang Li); https://orcid.org/0000-0003-2752-1925 (Qingguo Wang) 

关键词: 脑, 免疫, 炎症, 相互作用, 缺血性脑卒中, 机制, 小胶质细胞, 神经元, 继发性损伤, T细胞

Abstract:

The primary mechanism of secondary injury after cerebral ischemia may be the brain inflammation that emerges after an ischemic stroke, which promotes neuronal death and inhibits nerve tissue regeneration. As the first immune cells to be activated after an ischemic stroke, microglia play an important immunomodulatory role in the progression of the condition. After an ischemic stroke, peripheral blood immune cells (mainly T cells) are recruited to the central nervous system by chemokines secreted by immune cells in the brain, where they interact with central nervous system cells (mainly microglia) to trigger a secondary neuroimmune response. This review summarizes the interactions between T cells and microglia in the immune-inflammatory processes of ischemic stroke. We found that, during ischemic stroke, T cells and microglia demonstrate a more pronounced synergistic effect. Th1, Th17, and M1 microglia can co-secrete pro-inflammatory factors, such as interferon-γ, tumor necrosis factor-α, and interleukin-1β, to promote neuroinflammation and exacerbate brain injury. Th2, Treg, and M2 microglia jointly secrete anti-inflammatory factors, such as interleukin-4, interleukin-10, and transforming growth factor-β, to inhibit the progression of neuroinflammation, as well as growth factors such as brain-derived neurotrophic factor to promote nerve regeneration and repair brain injury. Immune interactions between microglia and T cells influence the direction of the subsequent neuroinflammation, which in turn determines the prognosis of ischemic stroke patients. Clinical trials have been conducted on the ways to modulate the interactions between T cells and microglia toward anti-inflammatory communication using the immunosuppressant fingolimod or overdosing with Treg cells to promote neural tissue repair and reduce the damage caused by ischemic stroke. However, such studies have been relatively infrequent, and clinical experience is still insufficient. In summary, in ischemic stroke, T cell subsets and activated microglia act synergistically to regulate inflammatory progression, mainly by secreting inflammatory factors. In the future, a key research direction for ischemic stroke treatment could be rooted in the enhancement of anti-inflammatory factor secretion by promoting the generation of Th2 and Treg cells, along with the activation of M2-type microglia. These approaches may alleviate neuroinflammation and facilitate the repair of neural tissues. 

Key words: brain, immune, inflammation, interaction, ischemic stroke, mechanism, microglia, neuron, secondary injury, T cells