Regulatory T cells suppress excessive lipid accumulation in alcoholic liver disease
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, d...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-05-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S002222752032263X |
| _version_ | 1818417903849963520 |
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| author | Hongwu Wang Ting Wu Yaqi Wang Xiaoyang Wan Junying Qi Lan Li Xiaojing Wang Xiaoping Luo Qin Ning |
| author_facet | Hongwu Wang Ting Wu Yaqi Wang Xiaoyang Wan Junying Qi Lan Li Xiaojing Wang Xiaoping Luo Qin Ning |
| author_sort | Hongwu Wang |
| collection | DOAJ |
| description | 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-α 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. |
| first_indexed | 2024-12-14T12:14:11Z |
| format | Article |
| id | doaj.art-effaae607db24da6992437273611cd20 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-14T12:14:11Z |
| publishDate | 2019-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-effaae607db24da6992437273611cd202022-12-21T23:01:41ZengElsevierJournal of Lipid Research0022-22752019-05-01605922936Regulatory T cells suppress excessive lipid accumulation in alcoholic liver diseaseHongwu Wang0Ting Wu1Yaqi Wang2Xiaoyang Wan3Junying Qi4Lan Li5Xiaojing Wang6Xiaoping Luo7Qin Ning8Institute of Infectious Disease Huazhong University of Science and Technology, Wuhan 430030, China; Departments of Infectious Disease Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartments of Infectious Disease Huazhong University of Science and Technology, Wuhan 430030, ChinaInstitute of Infectious Disease Huazhong University of Science and Technology, Wuhan 430030, ChinaInstitute of Infectious Disease Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartments of Infectious Disease Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartments of Infectious Disease Huazhong University of Science and Technology, Wuhan 430030, ChinaInstitute of Infectious Disease Huazhong University of Science and Technology, Wuhan 430030, ChinaPediatrics Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaTo whom correspondence should be addressed.; Institute of Infectious Disease Huazhong University of Science and Technology, Wuhan 430030, China; Departments of Infectious Disease Huazhong University of Science and Technology, Wuhan 430030, China; To whom correspondence should be addressed.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-α 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.http://www.sciencedirect.com/science/article/pii/S002222752032263Xalcoholic fatty liverlipid metabolismmonocyte chemoattractant protein-1tumor necrosis factor-α |
| spellingShingle | Hongwu Wang Ting Wu Yaqi Wang Xiaoyang Wan Junying Qi Lan Li Xiaojing Wang Xiaoping Luo Qin Ning Regulatory T cells suppress excessive lipid accumulation in alcoholic liver disease Journal of Lipid Research alcoholic fatty liver lipid metabolism monocyte chemoattractant protein-1 tumor necrosis factor-α |
| title | Regulatory T cells suppress excessive lipid accumulation in alcoholic liver disease |
| title_full | Regulatory T cells suppress excessive lipid accumulation in alcoholic liver disease |
| title_fullStr | Regulatory T cells suppress excessive lipid accumulation in alcoholic liver disease |
| title_full_unstemmed | Regulatory T cells suppress excessive lipid accumulation in alcoholic liver disease |
| title_short | Regulatory T cells suppress excessive lipid accumulation in alcoholic liver disease |
| title_sort | regulatory t cells suppress excessive lipid accumulation in alcoholic liver disease |
| topic | alcoholic fatty liver lipid metabolism monocyte chemoattractant protein-1 tumor necrosis factor-α |
| url | http://www.sciencedirect.com/science/article/pii/S002222752032263X |
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