Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis, MN.
Department of Immunology, University of Toronto, Toronto, ON, Canada.
Hepatology. 2021 Oct;74(4):2277-2286. doi: 10.1002/hep.31889. Epub 2021 Jun 18.
NAFLD is one of the leading causes of abnormal liver function worldwide. NAFLD refers to a group of liver conditions ranging from nonalcoholic fatty liver to NASH, which involves inflammation, hepatocellular damage, and fibrosis. Triggering of inflammation in NASH is a key event in the progression of the disease, and identifying the factors that initiate or dysregulate this process is needed to develop strategies for its prevention or treatment. B cells have been implicated in several autoimmune and inflammatory diseases. However, their role in the pathogenesis of NAFLD and NASH is less clear. This review discusses the emerging evidence implicating intrahepatic B cells in the progression of NAFLD. We highlight the potential mechanisms of B-cell activation during NAFLD, such as increased hepatic expression of B-cell-activating factor, augmented oxidative stress, and translocation of gut-derived microbial products. We discuss the possible effector functions by which B cells promote NAFLD, including the production of proinflammatory cytokines and regulation of intrahepatic T cells and macrophages. Finally, we highlight the role of regulatory and IgA B cells in the pathogenesis of NASH-associated HCC. In this review, we make the case that future research is needed to investigate the potential of B-cell-targeting strategies for the treatment of NAFLD.
非酒精性脂肪性肝病（NAFLD）是全球范围内导致肝功能异常的主要原因之一。NAFLD 是指一组从非酒精性脂肪肝到 NASH 的肝脏疾病，其涉及炎症、肝细胞损伤和纤维化。NASH 中的炎症触发是非酒精性脂肪性肝病进展的关键事件，需要确定引发或失调该过程的因素，以便制定预防或治疗策略。B 细胞已被牵连到多种自身免疫和炎症性疾病中。然而，其在非酒精性脂肪性肝病和 NASH 发病机制中的作用尚不明确。本综述讨论了越来越多的证据表明肝内 B 细胞参与了非酒精性脂肪性肝病的进展。我们强调了 B 细胞在非酒精性脂肪性肝病期间激活的潜在机制，例如 B 细胞激活因子在肝脏中的表达增加、氧化应激增强和肠道来源的微生物产物易位。我们讨论了 B 细胞促进非酒精性脂肪性肝病的可能效应功能，包括产生促炎细胞因子以及调节肝内 T 细胞和巨噬细胞。最后，我们强调了调节性和 IgA B 细胞在 NASH 相关 HCC 发病机制中的作用。在本综述中，我们提出需要进行未来的研究来探讨针对非酒精性脂肪性肝病的 B 细胞靶向治疗策略的潜力。
