Research Progress on the Role of Immune Cell Dysfunction in the Occurrence and Development of Liver Failure
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摘要: 肝脏作为人体核心代谢器官，承担着蛋白质合成、毒物代谢、免疫调节等多种关键生理功能。肝衰竭是终末期肝病患者的主要疾病进程，临床特征包括凝血功能障碍、胆红素代谢异常以及多器官衰竭。根据病程的不同，肝衰竭可分为急性、亚急性、慢加急性及慢性四类，其致病机制复杂，涉及病原感染、免疫微环境的失调和肠道菌群紊乱等多种因素的相互作用，给临床诊治带来了巨大挑战。本文综述了肝衰竭在发生发展过程中天然和适应性免疫应答异常，以及免疫代谢紊乱的分子机制，深入探讨免疫细胞的功能紊乱在该疾病过程中的关键作用，旨在为肝衰竭的靶向免疫治疗提供理论依据。Abstract: The liver, as the core metabolic organ of the human body, undertakes multiple critical physiological functions such as protein synthesis, xenobiotic metabolism, and immune regulation. Liver failure represents a major disease process in patients with end-stage liver disease, characterized clinically by coagulopathy, abnormal bilirubin metabolism, and multiple organ dysfunction. Depending on the disease course, liver failure can be classified into four types: acute, subacute, acute-on-chronic, and chronic. The pathogenic mechanisms are complex, involving interactions among various factors such as pathogen infections, dysregulation of the immune microenvironment, and gut microbiota disturbances, which pose significant challenges for clinical diagnosis and treatment. This review summarizes the abnormalities in innate and adaptive immune responses, as well as the molecular mechanisms of immune metabolic dysregulation during the occurrence and progression of liver failure. It further explores the pivotal role of immune cell dysfunction in the disease process, aiming to provide a theoretical basis for targeted immune therapies in liver failure.
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Key words:
- Liver failure /
- Immune cell function /
- Immune response /
- Immunometabolism /
- Targeted therapy
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图 1 肝衰竭免疫病理发生发展时序图
注：肝衰竭患者中，先天和适应性免疫相互作用过度炎症和免疫抑制共存，引发多器官损伤。其中
Figure 1. Timeline of the immunopathogenesis of liver failure
图 2 免疫细胞在肝衰中的作用机制
注：NET：中性粒细胞胞外诱捕网；MerTK：MER受体酪氨酸激酶；TERM-2：髓系细胞触发受体2；EZH2：Zeste同源物增强子2；SOCS1：细胞因子信号抑制物1；KCTD9：钾通道四聚体结构域9；BTLA：B和T淋巴细胞弱化因子；VISTA：T细胞激活抑制物免疫球蛋白可变区结构域。
Figure 2. The mechanism of immune cells in liver failure
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