Department of Hepatology and Gastroenterology, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin, Germany.
Berlin Institute of Health at Charité - Universitätsmedizin Berlin, BIH Biomedical Innovation Academy, BIH Charité Digital Clinician Scientist Program, Berlin, Germany.
Results Probl Cell Differ. 2024;74:175-209. doi: 10.1007/978-3-031-65944-7_7.
The liver fulfils a plethora of metabolic and immunological functions. Liver macrophages are a heterogeneous immune cell population with high plasticity and are important for maintaining normal liver function but are also critically involved in disease processes. In this chapter, we review the heterogeneity and multifaceted functions of hepatic macrophages in liver health and in disease conditions, including acute liver injury, chronic liver diseases, and hepatocellular carcinoma. Under homeostatic conditions, the tissue resident Kupffer cells are phagocytic cells that have important functions in immune surveillance, antigen presentation, and metabolic regulation while the roles of other populations such as capsular, peritoneal, or monocyte-derived macrophages in liver health are less clearly defined. Upon liver injury, Kupffer cell numbers are markedly reduced while monocyte-derived macrophages significantly expand and take critical roles in driving and resolving liver injury, including important pathogenic involvements in inflammation, fibrosis, and regeneration. They also create and maintain an immunosuppressive and immune-excluded microenvironment in hepatocellular carcinoma. Single-cell and spatial omics technologies are significantly expanding our understanding of the diversity and plasticity of macrophage populations under different conditions and enable the reliable identification of specific hepatic macrophage subsets. This knowledge can now be applied to dissect the exact contributions of distinct macrophage populations to disease processes and hopefully will pave the way for new therapeutic interventions.
肝脏具有多种代谢和免疫功能。肝脏巨噬细胞是一种异质性的免疫细胞群体,具有高度的可塑性,对于维持正常的肝功能非常重要,但也在疾病过程中起着至关重要的作用。在本章中,我们综述了肝脏巨噬细胞在肝脏健康和疾病状态下的异质性和多方面功能,包括急性肝损伤、慢性肝病和肝细胞癌。在稳态条件下,组织驻留的库普弗细胞是吞噬细胞,在免疫监视、抗原呈递和代谢调节方面具有重要功能,而其他群体(如包膜、腹膜或单核细胞衍生的巨噬细胞)在肝脏健康中的作用则不太明确。在肝损伤时,库普弗细胞数量明显减少,而单核细胞衍生的巨噬细胞显著扩增,并在驱动和解决肝损伤中发挥关键作用,包括在炎症、纤维化和再生中的重要致病作用。它们还在肝细胞癌中形成和维持免疫抑制和免疫排斥的微环境。单细胞和空间组学技术极大地扩展了我们对不同条件下巨噬细胞群体多样性和可塑性的理解,并能够可靠地识别特定的肝脏巨噬细胞亚群。这些知识现在可以用于剖析不同巨噬细胞群体对疾病过程的确切贡献,并有望为新的治疗干预铺平道路。
Results Probl Cell Differ. 2024
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