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小胶质细胞固有免疫记忆的表观遗传调节与神经系统疾病

周锦涛, 俞仲望, 曹莉^*

海军军医大学基础医学院神经生物学教研室，上海 200433

摘要

小胶质细胞具有介导固有免疫记忆的能力，可由初级刺激引起小胶质细胞重编程，从而增强或抑制小胶质细胞对次级刺激的免疫反应。炎症刺激是小胶质细胞产生固有免疫记忆的重要因素，单一或重复的炎症刺激是小胶质细胞形成不同细胞表型的诱因。小胶质细胞介导固有免疫反应过程中涉及许多免疫记忆调控。免疫记忆调控是多方面综合作用的结果。增强子修饰是小胶质细胞表观遗传调控的关键途径，H3K27ac增强子标记与免疫训练形成密切相关。细胞因子TGF-β1介导IL-10和IL-1β之间的相互作用，从而影响小胶质细胞表型。小胶质细胞糖酵解活性在免疫训练形成后增强，而氧化磷酸化与免疫耐受形成有关。固有免疫记忆与神经退行性疾病、脑肿瘤、脑损伤和精神疾病密切相关。深入研究小胶质细胞介导固有免疫反应的机制有助于加强对中枢神经系统疾病发生和发展的进一步认识，也有助于为治疗中枢神经系统疾病提供新思路。

关键词： 小胶质细胞; 固有免疫记忆; 表观遗传修饰; 细胞因子; 代谢通路; 中枢神经系统疾病

Epigenetic regulation of microglia-mediated innate immune memory and neurological diseases

ZHOU Jin-Tao, YU Zhong-Wang, CAO Li^*

Department of Neurobiology, College of Basic Medical Sciences, Naval Medical University, Shanghai 200433, China

Abstract

Microglia have the ability to mediate innate immune memory and can be reprogrammed by primary stimuli to enhance or inhibit the immune response of microglia to secondary stimuli. Inflammatory stimulation is an important factor for microglia to mediate innate immune memory. Single or repeated stimulation can induce microglia to form different phenotypes. Microglia-mediated innate immune response is involved in the regulation of immune memory. Enhancer modification is a key pathway of microglia epigenetic regulation, and the H3K27ac enhancer marker is closely related to immune training. TGF-β1 mediates the interaction between IL-10 and IL-1β, thereby influencing the microglial phenotype. Microglia glycolysis activity is increased after immune training, and oxidative phosphorylation is associated with immune tolerance. Innate immune memory is closely associated with neurodegenerative diseases, brain tumors, brain damage and psychosis. Further study on the mechanism of microglia-mediated innate immune memory is helpful to understand the occurrence and development of central nervous system diseases and provide new options for the treatment of central nervous system diseases.

Key words: microglia; innate immune memory; epigenetic modification; cytokine; metabolic pathways; central nervous system disease

收稿日期：　　录用日期：

通讯作者：曹莉　　E-mail: caoli@smmu.edu.cn

引用本文：

周锦涛, 俞仲望, 曹莉. 小胶质细胞固有免疫记忆的表观遗传调节与神经系统疾病[J]. 生理学报 2022; 74 (6): 1031-1038.

ZHOU Jin-Tao, YU Zhong-Wang, CAO Li. Epigenetic regulation of microglia-mediated innate immune memory and neurological diseases. Acta Physiol Sin 2022; 74 (6): 1031-1038 (in Chinese with English abstract).