Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei, China.
Front Immunol. 2022 Jul 22;13:951406. doi: 10.3389/fimmu.2022.951406. eCollection 2022.
Liver disease and its complications affect millions of people worldwide. NAFLD (non-alcoholic fatty liver disease) is the liver disease associated with metabolic dysfunction and consists of four stages: steatosis with or without mild inflammation (NAFLD), non-alcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. With increased necroinflammation and progression of liver fibrosis, NAFLD may progress to cirrhosis or even hepatocellular carcinoma. Although the underlying mechanisms have not been clearly elucidated in detail, what is clear is that complex immune responses are involved in the pathogenesis of NASH, activation of the innate immune system is critically involved in triggering and amplifying hepatic inflammation and fibrosis in NAFLD/NASH. Additionally, disruption of endoplasmic reticulum (ER) homeostasis in cells, also known as ER stress, triggers the unfolded protein response (UPR) which has been shown to be involved to inflammation and apoptosis. To further develop the prevention and treatment of NAFLD/NASH, it is imperative to clarify the relationship between NAFLD/NASH and innate immune cells and ER stress. As such, this review focuses on innate immune cells and their ER stress in the occurrence of NAFLD and the progression of cirrhosis.
肝脏疾病及其并发症影响着全球数百万人。非酒精性脂肪性肝病（NAFLD）是与代谢功能障碍相关的肝脏疾病，它由四个阶段组成：伴有或不伴有轻度炎症的脂肪变性（NAFLD）、非酒精性脂肪性肝炎（NASH）、纤维化和肝硬化。随着坏死性炎症和肝纤维化的进展，NAFLD 可能进展为肝硬化，甚至肝细胞癌。尽管其潜在机制尚未详细阐明，但可以明确的是，复杂的免疫反应参与了 NASH 的发病机制，固有免疫系统的激活在触发和放大 NAFLD/NASH 中的肝炎症和纤维化方面起着至关重要的作用。此外，细胞内质网（ER）稳态的破坏，也称为 ER 应激，会引发未折叠蛋白反应（UPR），现已表明该反应与炎症和细胞凋亡有关。为了进一步开发预防和治疗 NAFLD/NASH 的方法，阐明 NAFLD/NASH 与固有免疫细胞和 ER 应激之间的关系至关重要。因此，本综述重点介绍固有免疫细胞及其在 NAFLD 发生和肝硬化进展中的 ER 应激。
