Li Honggui, Guo Xinlei, Aquino Eduardo, Wu Chaodong
Department of Nutrition, Texas A&M University, College Station, TX, United States.
Front Nutr. 2023 Mar 1;10:1139339. doi: 10.3389/fnut.2023.1139339. eCollection 2023.
Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic diseases serving as a major threat to human health. While the pathogenesis of NAFLD is multi-factorial, inflammation is considered a critical factor driving the development and progression of NAFLD phenotype, including liver fibrosis. As an essential mediator of innate immunity, stimulator of interferon genes (STING) functions to promote anti-viral immunity. Accumulating evidence also indicates that STING functions to promote the proinflammatory activation of several types of liver cells, especially macrophages/Kupffer cells, in a manner independent of interferon production. Over the past several years, a significant body of literature has validated a detrimental role for STING in regulating the pathogenesis of hepatic steatosis and inflammation. In particular, the STING in macrophages/Kupffer cells has attracted much attention due to its importance in not only enhancing macrophage proinflammatory activation, but also generating macrophage-derived mediators to increase hepatocyte fat deposition and proinflammatory responses, and to activate hepatic stellate cell fibrogenic activation. Both intracellular and extracellular signals are participating in STING activation in macrophages, thereby critically contributing to NAFLD phenotype. This mini review summarizes recent advances on how STING is activated in macrophages in the context of NAFLD pathophysiology.
非酒精性脂肪性肝病（NAFLD）是最常见的慢性疾病之一，对人类健康构成重大威胁。虽然NAFLD的发病机制是多因素的，但炎症被认为是驱动NAFLD表型发展和进展（包括肝纤维化）的关键因素。作为固有免疫的重要介质，干扰素基因刺激物（STING）具有促进抗病毒免疫的功能。越来越多的证据还表明，STING以独立于干扰素产生的方式促进几种类型肝细胞（尤其是巨噬细胞/库普弗细胞）的促炎激活。在过去几年中，大量文献证实了STING在调节肝脂肪变性和炎症发病机制中具有有害作用。特别是，巨噬细胞/库普弗细胞中的STING因其不仅在增强巨噬细胞促炎激活方面很重要，而且在产生巨噬细胞衍生介质以增加肝细胞脂肪沉积和促炎反应以及激活肝星状细胞纤维化激活方面的重要性而备受关注。细胞内和细胞外信号都参与巨噬细胞中STING的激活，从而对NAFLD表型起关键作用。本综述总结了在NAFLD病理生理学背景下巨噬细胞中STING如何被激活的最新进展。
