Yang Liu, Hao Yawen, Boeckmans Joost, Rodrigues Robim M, He Yong
Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai, China; University of Chinese Academy of Sciences, Beijing, China.
Department of In Vitro Toxicology and Dermato-Cosmetology, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium.
Pharmacol Ther. 2023 Mar;243:108353. doi: 10.1016/j.pharmthera.2023.108353. Epub 2023 Feb 2.
Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease worldwide. Despite extensive research and multiple clinical trials, there are still no FDA-approved therapies to treat the most severe forms of NAFLD. This is largely due to its complicated etiology and pathogenesis, which involves visceral obesity, insulin resistance, gut dysbiosis, etc. Although inflammation is generally believed to be one of the critical factors that drive the progression of simple steatosis to nonalcoholic steatohepatitis (NASH), the exact type of inflammation and how it contributes to NASH pathogenesis remain largely unknown. Liver inflammation is accompanied by the elevation of inflammatory mediators, including cytokines and chemokines and consequently intrahepatic infiltration of multiple types of immune cells. Recent studies revealed that extracellular vesicles (EVs) derived from inflammatory cells and hepatocytes play an important role in controlling liver inflammation during NASH. In this review, we highlight the roles of innate and adaptive immune cells and their microRNA-enriched EVs during NAFLD development and discuss potential drugs that target inflammatory pathways for the treatment of NAFLD.
非酒精性脂肪性肝病（NAFLD）是全球慢性肝病的主要病因。尽管进行了广泛的研究和多项临床试验，但目前仍没有获得美国食品药品监督管理局（FDA）批准的治疗最严重形式NAFLD的疗法。这主要是由于其复杂的病因和发病机制，涉及内脏肥胖、胰岛素抵抗、肠道菌群失调等。虽然炎症通常被认为是推动单纯性脂肪变性发展为非酒精性脂肪性肝炎（NASH）的关键因素之一，但炎症的确切类型及其如何促进NASH发病机制在很大程度上仍不清楚。肝脏炎症伴随着炎症介质的升高，包括细胞因子和趋化因子，进而导致多种类型免疫细胞的肝内浸润。最近的研究表明，源自炎症细胞和肝细胞的细胞外囊泡（EVs）在NASH期间控制肝脏炎症中起重要作用。在这篇综述中，我们强调先天性和适应性免疫细胞及其富含微小RNA的EVs在NAFLD发展过程中的作用，并讨论针对炎症途径治疗NAFLD的潜在药物。
