代谢相关脂肪肝病（MAFLD）是一系列临床表现，从良性脂肪变性到肝硬化。 MAFLD 病理生理学的一个关键事件是非酒精性脂肪性肝炎 (NASH) 的发展，它可能导致纤维化和肝细胞癌，但 MAFLD 相关炎症的触发因素尚不清楚。我们观察到肝细胞中的脂质积累会诱导激活免疫受体 NKG2D 特异性配体的表达。组织驻留的先天样 T 细胞，尤其是 γδ T 细胞，通过 NKG2D 激活并分泌 IL-17A。 IL-17A 允许肝细胞产生趋化因子，将促炎细胞招募到肝脏中，从而导致 NASH 和纤维化。 NKG2D 缺陷小鼠在 NASH 饮食模型中不会出现纤维化，并且肝肿瘤发生率降低。 MAFLD 患者血液中 IL-17A γδ T 细胞的频率与肝脏病理直接相关。我们的研究结果确定了一个关键的分子机制，在 MAFLD 背景下，应激肝细胞通过该机制引发炎症。

Metabolic-associated fatty liver disease (MAFLD) is a spectrum of clinical manifestations ranging from benign steatosis to cirrhosis. A key event in the pathophysiology of MAFLD is the development of nonalcoholic steatohepatitis (NASH), which can potentially lead to fibrosis and hepatocellular carcinoma, but the triggers of MAFLD-associated inflammation are not well understood. We have observed that lipid accumulation in hepatocytes induces expression of ligands specific to the activating immune receptor NKG2D. Tissue-resident innate-like T cells, most notably γδ T cells, are activated through NKG2D and secrete IL-17A. IL-17A licenses hepatocytes to produce chemokines that recruit proinflammatory cells into the liver, which causes NASH and fibrosis. NKG2D-deficient mice did not develop fibrosis in dietary models of NASH and had a decreased incidence of hepatic tumors. The frequency of IL-17A+ γδ T cells in the blood of patients with MAFLD correlated directly with liver pathology. Our findings identify a key molecular mechanism through which stressed hepatocytes trigger inflammation in the context of MAFLD.