Wang Hongwu, Wu Ting, Wang Yaqi, Wan Xiaoyang, Qi Junying, Li Lan, Wang Xiaojing, Luo Xiaoping, Ning Qin
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.
Departments of Infectious Disease Huazhong University of Science and Technology, Wuhan 430030, China.
J Lipid Res. 2019 May;60(5):922-936. doi: 10.1194/jlr.M083568. Epub 2019 Feb 21.
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.
长期饮酒导致肝脏免疫细胞致敏，引发炎症细胞积聚，这被认为是肝损伤的主要原因。调节性T细胞（Tregs）是一种免疫抑制细胞亚群，在多种肝脏疾病中发挥重要作用；然而，关于Tregs在酒精性肝病（ALD）肝脂肪变性中的病理参与的数据并不充分。在ALD小鼠模型中，我们发现长期饮酒导致肝脏脂质蓄积增加，同时伴有氧化应激、炎症细胞积聚和Tregs减少。Tregs的过继转移缓解了脂质代谢紊乱、氧化应激和炎症，从而改善了酒精性脂肪肝。巨噬细胞是ALD中炎症的主要来源。长期饮酒期间，巨噬细胞异常激活和细胞因子产生被激活，但Treg转移后显著受到抑制。在体外，酒精和脂多糖共同激活巨噬细胞，以模拟酒精性肝微环境。Tregs抑制这些巨噬细胞产生单核细胞趋化蛋白-1和TNF-α。然而，当白细胞介素（IL）-10被阻断时，Tregs的这种作用被显著中和。总之，我们的数据揭示了Tregs在恢复ALD肝脏脂质代谢中的新作用，这部分依赖于IL-10介导的对肝脏促炎巨噬细胞的抑制。
