DOI：10.1038/nature16969 作者：Tim F. Greten
摘要 : 非酒精性脂肪肝(NAFLD)是慢性肝病的最普遍病因之一，被认为是从代谢上来讲易导致肝癌的一个因素。
非酒精性脂肪肝(NAFLD)是慢性肝病的最普遍病因之一，被认为是从代谢上来讲易导致肝癌的一个因素。利用小鼠模型和来自NAFLD患者及健康对照组的样本，Tim Greten及同事显示，NAFLD通过亚油酸的生成、线粒体功能的破坏和CD4+ T-细胞的选择性丢失来促进肝细胞癌变，导致抗肿瘤免疫能力降低。
Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death. Non-alcoholic fatty liver disease (NAFLD) affects a large proportion of the US population and is considered to be a metabolic predisposition to liver cancer1, 2, 3, 4, 5. However, the role of adaptive immune responses in NAFLD-promoted HCC is largely unknown. Here we show, in mouse models and human samples, that dysregulation of lipid metabolism in NAFLD causes a selective loss of intrahepatic CD4+ but not CD8+ T lymphocytes, leading to accelerated hepatocarcinogenesis. We also demonstrate that CD4+ T lymphocytes have greater mitochondrial mass than CD8+ T lymphocytes and generate higher levels of mitochondrially derived reactive oxygen species (ROS). Disruption of mitochondrial function by linoleic acid, a fatty acid accumulated in NAFLD, causes more oxidative damage than other free fatty acids such as palmitic acid, and mediates selective loss of intrahepatic CD4+ T lymphocytes. In vivo blockade of ROS reversed NAFLD-induced hepatic CD4+ T lymphocyte decrease and delayed NAFLD-promoted HCC. Our results provide an unexpected link between lipid dysregulation and impaired anti-tumour surveillance.
来源： Nature 浏览次数：0