Transcriptomics

Dataset Information

2

Non-alcoholic steatohepatitis causes selective CD4+ T cell loss and promotes hepatocarcinogenesis


ABSTRACT: Hepatocellular carcinoma (HCC) is the second most common cause of cancer related death. NAFLD affects a large proportion of the US population. Its incidence and prevalence are increasing to epidemic proportions around the world and is known to increase the risk of HCC. We studied how intrahepatic lipids affect adaptive immunity and HCC development in different murine models of NASH and HCC. Linoleic acid, a fatty acid found in NAFLD caused a selective loss of hepatic CD4+ but not CD8+ T cells leading to accelerated hepatocarcinogenesis. CD4+ T cells were more dependent on oxidative phosphorylation for energy source than CD8+ T cells, and disruption of oxidative phosphorylation by linoleic acid caused more severe damage in CD4+ T cells leading to selective loss of these cells. In vivo blockade of ROS using n-acetylcysteine reversed the NASH-induced hepatic CD4+ T cell decrease and delayed NASH-promoted HCC. Our results provide a new link between lipid metabolism and impaired anti-tumor surveillance. The samples are isolated CD4 or CD8 T cells co-cultured with linoleic acid or not. The aim of the particular experiment is to study the any possible different response between CD4 and CD8 T cells to linoleic acid.

ORGANISM(S): Mus musculus  

SUBMITTER: Masaki Terabe   Armin Weber  Veena Kapoor  Tim F Greten  Tobias Eggert  David Kleiner  Dean W Felsher  Chi Ma  Giorgio Trinchieri  Daniel W McVicar  Jose Medina-Echeverz  Aparna H Kesarwala  Mathias Heikenwälder  Mei ElGindi  PING JIN  David F Stroncek  Miaojun Han  Ping Jin 

PROVIDER: E-GEOD-67918 | ArrayExpress | 2016-03-10

SECONDARY ACCESSION(S): GSE67918PRJNA281238

REPOSITORIES: GEO, ArrayExpress

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Publications


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 lymp  ...[more]

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