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Regulatory T cells suppress excessive lipid accumulation in alcoholic liver disease.

ABSTRACT: Sensitization of hepatic immune cells from chronic alcohol consumption gives rise to inflammatory accumulation, which is considered a leading cause of liver damage. Regulatory T cells (Tregs) are an immunosuppressive cell subset that plays an important role in a variety of liver diseases; however, data about pathological involvement of Tregs in liver steatosis of alcoholic liver disease (ALD) is insufficient. In mouse models of ALD, we found that increased lipid accumulation by chronic alcohol intake was accompanied by oxidative stress, inflammatory accumulation, and Treg decline in the liver. Adoptive transfer of Tregs relieved lipid metabolic disorder, oxidative stress, inflammation, and, consequently, ameliorated the alcoholic fatty liver. Macrophages are a dominant source of inflammation in ALD. Aberrant macrophage activation and cytokine production were activated during chronic alcohol consumption, but were significantly inhibited after Treg transfer. In vitro, macrophages were co-activated by alcohol and lipopolysaccharide to mimic a condition for alcoholic liver microenvironment. Tregs suppressed monocyte chemoattractant protein-1 and TNF-? production from these macrophages. However, such effects of Tregs were remarkably neutralized when interleukin (IL)-10 was blocked. Altogether, our data uncover a novel role of Tregs in restoring liver lipid metabolism in ALD, which partially relies on IL-10-mediated suppression of hepatic pro-inflammatory macrophages.

SUBMITTER: Wang H

PROVIDER: S-EPMC6495164 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Regulatory T cells suppress excessive lipid accumulation in alcoholic liver disease.

Wang Hongwu H Wu Ting T Wang Yaqi Y Wan Xiaoyang X Qi Junying J Li Lan L Wang Xiaojing X Luo Xiaoping X Ning Qin Q

Journal of lipid research 20190221 5

Sensitization of hepatic immune cells from chronic alcohol consumption gives rise to inflammatory accumulation, which is considered a leading cause of liver damage. Regulatory T cells (Tregs) are an immunosuppressive cell subset that plays an important role in a variety of liver diseases; however, data about pathological involvement of Tregs in liver steatosis of alcoholic liver disease (ALD) is insufficient. In mouse models of ALD, we found that increased lipid accumulation by chronic alcohol i ...[more]

PMID: 30792182

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Project description:Chronic alcohol intake leads to alcoholic fatty liver. The pathogenesis of alcoholic fatty liver is related to abnormal lipid accumulation, oxidative stress, endotoxins, and cytokines. Solanum muricatum Ait. (Pepino) is a plant food commonly cultivated in the Penghu island, Taiwan. Previous studies indicated that the aqueous extract of pepino was able to attenuate diabetic progression via its antioxidative and anti-inflammatory effects. However, the mechanisms of the antioxidative and anti-inflammatory effects of pepino leaf in preventing alcoholic fatty liver remain unknown. In this study, Lieber?DeCarli ethanol-containing liquid diet was used to induce alcoholic hepatic injury in C57BL/6 mice. The hepatoprotective effects and the related mechanisms of aqueous extract of pepino leaf (AEPL) were examined. Our results showed that 2% AEPL treatments protected the liver from ethanol-induced injury through reducing serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC) and triglyceride (TG) (all p < 0.05). AEPL had the effects in improving the ethanol-induced lipid accumulation in mice under histological examination. Molecular data indicated that the anti-lipid accumulation effect of AEPL might be mediated via inducing hepatic levels of phospho-adenosine monophosphate-activated kinase (p-AMPK) and peroxisome proliferator-activated receptor (PPAR)-?, and reducing the expressions of hepatic lipogenic enzymes, including sterol regulatory element-binding protein (SREBP)-1c, acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS) (all p < 0.05). AEPL also decreased hepatic levels of thiobarbituric acid relative substances (TBARS), tumor necrosis factor (TNF)-?, and interleukin (IL)-6, as well as the expression of nuclear factor kappa B (NF-?B) (all p < 0.05). Moreover, AEPL significantly elevated the activities of superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx), and glutathione (GSH) content compared to the ethanol-fed group (all p < 0.05). Our present study suggests that AEPL could protect the liver against ethanol-induced oxidative injury and lipid accumulation.

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Regulatory T cells suppress excessive lipid accumulation in alcoholic liver disease.

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Regulatory T cells suppress excessive lipid accumulation in alcoholic liver disease.

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