NKG2D公司
纤维化
炎症
脂肪性肝炎
脂肪肝
促炎细胞因子
先天免疫系统
非酒精性脂肪肝
生物
肝星状细胞
肝硬化
免疫学
癌症研究
脂肪变性
免疫系统
医学
病理
疾病
内科学
内分泌学
细胞毒性T细胞
体外
生物化学
作者
Sonja Marinović,Maja Lenartić,Karlo Mladenić,Marko Šestan,Inga Kavazović,Ante Benić,Mia Krapić,Lukas Rindlisbacher,Maja Cokarić Brdov̌ak,Colin Sparano,Gioana Litscher,Tamara Turk Wensveen,Ivana Mikolašević,Dora Fǔkar Čupić,Lidija Bilić-Zulle,Alexander Steinle,Ari Waisman,Adrian Hayday,Sònia Tugues,Burkhard Becher,Bojan Polić,Felix M. Wensveen
出处
期刊:Science immunology
[American Association for the Advancement of Science (AAAS)]
日期:2023-09-29
卷期号:8 (87)
被引量:2
标识
DOI:10.1126/sciimmunol.add1599
摘要
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.
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