Department of Pharmacology, University Medical Center, Johannes Gutenberg University, Mainz, Germany.
Front Immunol. 2024 Sep 20;15:1447391. doi: 10.3389/fimmu.2024.1447391. eCollection 2024.
Recent evidence suggests that adaptive immune cells are important contributors to metabolic dysfunction-associated steatotic liver disease (MASLD, formerly non-alcoholic fatty liver disease, NAFLD). In liver biopsies from MASLD patients, the accumulation of intrahepatic B cells is positively correlated with the MASLD activity score. Hepatic B-cell infiltration is observed in experimental models of metabolic dysfunction-associated steatohepatitis (MASH, formerly non-alcoholic steatohepatitis, NASH). Intrahepatic B2 cells have been shown to contribute to MASLD/MASH by activating T cells, macrophages and hepatic stellate cells, and by producing pathogenic IgG antibodies. In mice fed a MASH diet, selective depletion of B2 cells reduces steatohepatitis and fibrosis. Intestinal B cells are metabolically activated in MASH and promote T-cell activation independently of TCR signaling. In addition, B cells have been shown to contribute to liver fibrosis by activating monocyte-derived macrophages through the secretion of IgA immunoglobulins. Furthermore, our recent study indicates that certain B cell subsets, very likely regulatory B cells, may play a protective role in MASLD. This review summarizes the molecular mechanisms of B cell functions and discusses future research directions on the different roles of B cells in MASLD and MASH.
最近的证据表明，适应性免疫细胞是代谢功能障碍相关脂肪性肝病（MASLD，以前称为非酒精性脂肪性肝病，NAFLD）的重要贡献者。在 MASLD 患者的肝活检中，肝内 B 细胞的积累与 MASLD 活动评分呈正相关。在代谢功能障碍相关脂肪性肝炎（MASH，以前称为非酒精性脂肪性肝炎，NASH）的实验模型中观察到肝内 B 细胞浸润。肝内 B2 细胞通过激活 T 细胞、巨噬细胞和肝星状细胞以及产生致病性 IgG 抗体，有助于 MASLD/MASH。在接受 MASH 饮食的小鼠中，选择性耗尽 B2 细胞可减少脂肪性肝炎和纤维化。MASH 中肠道 B 细胞被代谢激活，并通过 TCR 信号独立促进 T 细胞激活。此外，B 细胞通过分泌 IgA 免疫球蛋白激活单核细胞衍生的巨噬细胞，从而有助于肝纤维化。此外，我们最近的研究表明，某些 B 细胞亚群（很可能是调节性 B 细胞）可能在 MASLD 中发挥保护作用。本综述总结了 B 细胞功能的分子机制，并讨论了 B 细胞在 MASLD 和 MASH 中不同作用的未来研究方向。
