NAFLD causes selective CD4(+) T lymphocyte loss and promotes hepatocarcinogenesis.
Nature
; 531(7593): 253-7, 2016 Mar 10.
Article
em En
| MEDLINE
| ID: mdl-26934227
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T CD4-Positivos
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Carcinoma Hepatocelular
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Carcinogênese
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Hepatopatia Gordurosa não Alcoólica
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Neoplasias Hepáticas
Tipo de estudo:
Etiology_studies
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Observational_studies
Idioma:
En
Revista:
Nature
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Estados Unidos