外源物诱导肝脏局部先天免疫反应的线粒体调控机制
Mitochondria-related mechanisms of hepatic local innate immune response induced by xenobiotics
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摘要:
肝脏作为体内代谢外源因素暴露最重要的器官之一，具有独特的血窦结构和丰富的免疫细胞亚群，构成了肝脏局部免疫微环境。其中，肝脏的先天免疫细胞既可通过清除病原体、抗原提呈作用参与宿主防御，还通过与肝实质细胞的相互作用参与外源因素介导的急性免疫反应、肝细胞毒性转归、慢性肝损伤以及肝致癌作用。线粒体作为细胞应激的关键靶细胞器，是整合肝脏局部免疫信号的分子互作平台，既通过线粒体质量控制精细调控细胞内的分子事件，也通过线粒体损伤相关分子模式介导不同细胞间通讯和交互作用调控免疫微环境的稳态。本文通过对参与肝脏局部免疫反应的先天免疫细胞亚群组成及其介导免疫反应级联的综述，阐述不同外源物诱导肝脏局部免疫的线粒体相关调控机制，为探讨经由肝脏局部免疫反应生物标志筛查和靶向干预以预防和控制肝脏损伤提供线索。
Abstract: As one of the most important metabolic organs for xenobiotcs, liver equips with a unique structure of sinusoids and various subsets of immune cells, forming a hepatic local immune microenvironment. Among them, hepatic innate immune cells not only participate in host defense via pathogen clearance and antgen presentaton, but also contribute to acute immune response, sequelae of hepatotoxicity, chronic liver injury, and carcinogenesis through the interactions with hepatocytes after xenobiotic exposure. Mitochondrion, a targeted organelle of cellular stress, is a molecular platorm for integratng immune signals, which fnely regulates cellular events by mitochondrial quality control and mediates cellular communication via mitochondrial damage-associated molecular paterns to regulate the immune microenvironment. This review summarized the composition of innate immune cells and the immune cascade mediated by hepatic local immunity, and elucidated the mitochondria-related mechanisms of hepatc local immunity induced by xenobiotcs, aiming to provide clues for screening biomarkers of hepatc local immunity and making targeted interventons against liver injury.
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