NAFLD causes selective CD4+ T lymphocyte loss and promotes hepatocarcinogenesis
By Chi Ma, A. Kesarwala, T. Eggert, J. Medina‐Echeverz, D. Kleiner, P. Jin, D. Stroncek, M. Terabe, V. Kapoor, Mei ElGindi and 10 more. Nature, 2016
693 citations recorded by the source corpus.
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 cancer. 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.
Subfields: Cell Biology, Epidemiology, Pathology and Forensic Medicine
View Paper: https://www.semanticscholar.org/paper/223a5ea6303fdf1dadddc69849da3d54016574b4
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Citations in the corpus
- The Role of Cancer-Associated Fibroblasts and Fibrosis in Liver Cancer (2016, background): “In NAFLD, there is a failure of CD4+ T cell–mediated immunosuppression, mediated by linoleic acid–induced mitochondrial ROS generation and subsequent loss of CD4+ T cells, resulting in increased hepatocarcinogenesis (22).”
- Palmitic Acid: Physiological Role, Metabolism and Nutritional Implications (2017, background): “In vivo blockade of reactive oxygen species inverted NAFLDinduced hepatic CD4+ T lymphocyte reduction and delayed NAFLD-induced hepatocellular carcinoma (Ma et al., 2016).”