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肠-肝-免疫轴:结构基础、细胞构筑、分子介质及疾病特异性表现

英文原题:The gut-liver-immune axis: structural basis, cellular architecture, molecular mediators, and disease-specific manifestations.

PubMed 2026/08/03(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

研究概要

肠道和肝脏通过门静脉循环、胆道、淋巴引流和神经免疫通路构成一个解剖和功能单元。

中文摘要

肠道和肝脏通过门静脉循环、胆道、淋巴引流和神经免疫通路构成一个解剖和功能单元。近年来,经典的肠-肝轴已从以微生物和代谢为主的概念扩展为更广泛的框架,其中免疫细胞被视为器官间信号传导的核心整合者。在健康状态下,平衡的微生物感知、完整的黏膜和血管屏障、受调控的胆汁酸信号以及特化的组织驻留免疫程序在肠道和肝脏界面维持免疫耐受。在疾病状态下,菌群失调、屏障失效、胆汁酸池改变、内源性肝毒性代谢物以及异常的免疫细胞迁移重塑肝脏免疫微环境,驱动脂肪性肝炎、酒精相关性肝损伤、胆管病、肝硬化、急性失代偿和肝细胞癌。本综述将肠-肝轴重新定义为肠-肝-免疫轴,并综合了关于其结构基础、细胞架构、分子介质和疾病特异性表现的当前证据。我们讨论了巨噬细胞、树突状细胞、中性粒细胞、固有样T细胞、NK 细胞和适应性T细胞亚群在将肠道来源信号转化为肝脏炎症、组织修复、纤维化或肿瘤监视中的作用。我们还强调了肝脏在塑造肠道免疫中的双向作用,特别是通过胆汁酸和肝胆来源介质。最后,我们审视了当前靶向微生物群、黏膜屏障、胆汁酸信号和免疫细胞迁移的治疗策略,并概述了应指导下一代机制和临床研究的主要概念性和转化性空白。

展开英文摘要原文

The gut and liver form an anatomical and functional unit linked by the portal circulation, the biliary tract, lymphatic drainage, and neuroimmune pathways. In recent years, the classical gut-liver axis has expanded from a predominantly microbial and metabolic concept into a broader framework in which immune cells are viewed as central integrators of inter-organ signaling. In health, balanced microbial sensing, intact mucosal and vascular barriers, regulated bile acid signaling, and specialized tissue-resident immune programs preserve tolerance at both intestinal and hepatic interfaces. In disease, dysbiosis, barrier failure, altered bile acid pools, endogenous hepatotoxic metabolites, and aberrant immune-cell trafficking remodel the hepatic immune niche and drive steatohepatitis, alcohol-associated liver injury, cholangiopathy, cirrhosis, acute decompensation, and hepatocellular carcinoma. This review reframes the gut-liver axis as a gut-liver-immune axis and synthesizes current evidence on its structural basis, cellular architecture, molecular mediators, and disease-specific manifestations. We discuss the roles of macrophages, dendritic cells, neutrophils, innate-like T cells, natural killer cells, and adaptive T-cell subsets in translating gut-derived signals into hepatic inflammation, tissue repair, fibrosis, or tumor surveillance. We also highlight the bidirectional role of the liver in shaping intestinal immunity, particularly through bile acids and hepatobiliary-derived mediators. Finally, we examine current therapeutic strategies targeting the microbiota, mucosal barrier, bile acid signaling, and immune-cell trafficking, and we outline major conceptual and translational gaps that should guide the next generation of mechanistic and clinical studies.

论文信息

作者
Yoon SJ、Eom JA、Suk KT
单位
Institute for Liver and Digestive Diseases, Hallym University College of Medicine, Chuncheon, Republic of Korea.South Korea
文献类型
综述
期刊
Frontiers in immunology2026
原文标识
PubMed 42666859 · DOI 10.3389/fimmu.2026.1864805