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Th17/Treg细胞失衡参与小鼠非酒精性脂肪性肝病的进展。

The imbalance of Th17/Treg cells is involved in the progression of nonalcoholic fatty liver disease in mice.

作者信息

He Beihui, Wu Liyan, Xie Wei, Shao Yitong, Jiang Jianping, Zhao Zhenzhong, Yan Maoxiang, Chen Zhiyun, Cui Dawei

机构信息

Laboratory of Digestive Disease, the First Affiliated Hospital of Zhejiang Chinese Medical University, 54,Youdian Road, Hangzhou, 310006, Zhejiang Province, People's Republic of China.

Department of Equipment, the Third People's Hospital of Hangzhou, 38,Westlake Road, Hangzhou, 310009, People's Republic of China.

出版信息

BMC Immunol. 2017 Jun 24;18(1):33. doi: 10.1186/s12865-017-0215-y.

Abstract

BACKGROUND

Non-alcoholic fatty liver disease (NAFLD) is a common, chronic liver disease worldwide. Recent studies have shown that T helper (Th) 17 and regulatory T (Treg) cells play critical roles in various disorders of liver inflammation. Here, we explored the value of polyene phosphatidylcholine capsules (PPC) for regulating the imbalance of Th17/Treg cells in the pathogenesis of mice with NAFLD.

METHODS

C57BL/6 mice were randomly divided into three groups as follows:normal diet (ND), high-fat diet (HF),and HF plus PPC(HF + PPC). The frequencies of splenic Th17 and Treg cells were measured by flow cytometry, and their related cytokines were analyzed by CBA and real-time PCR.

RESULTS

At the end of 24 weeks, mice in the HF group had a higher frequency of intrahepatic Th17 cells,and a lower proportion of Treg cells compared with the ND group. The levels of Th17 cell-related cytokines (IL-6, IL-17 and IL-23) in serum and in liver tisse were increased,and the hepatic mRNA levels of RORγt, STAT3 and IL-6 were also increased. By contrast,the FoxP3 mRNA level was decreased in the HF group. Moreover, significant pathological and biochemical changes in the liver, as well as serum biochemical changes, were found in mice with NAFLD. Interestingly, following treatment with PPC, the levels of liver inflammation,frequencies of Th17/Treg cells and associated cytokines,and biochemical data were significantly altered.

CONCLUSION

These findings demonstrate a critical role for PPC in partially attenuating liver inflammatory responses in mice with NAFLD that involves the imbalance of Treg/Th17 cells and associated cytokines.

摘要

背景

非酒精性脂肪性肝病(NAFLD)是一种全球常见的慢性肝病。最近的研究表明,辅助性T细胞(Th)17和调节性T(Treg)细胞在各种肝脏炎症性疾病中起关键作用。在此,我们探讨了多烯磷脂酰胆碱胶囊(PPC)在调节NAFLD小鼠发病机制中Th17/Treg细胞失衡方面的价值。

方法

将C57BL/6小鼠随机分为三组:正常饮食(ND)组、高脂饮食(HF)组和高脂饮食加PPC(HF+PPC)组。通过流式细胞术检测脾Th17和Treg细胞的频率,并通过CBA和实时PCR分析其相关细胞因子。

结果

24周结束时,与ND组相比,HF组小鼠肝内Th17细胞频率更高,Treg细胞比例更低。血清和肝组织中Th17细胞相关细胞因子(IL-6、IL-17和IL-23)水平升高,肝脏中RORγt、STAT3和IL-6的mRNA水平也升高。相比之下,HF组FoxP3 mRNA水平降低。此外,NAFLD小鼠肝脏出现明显的病理和生化变化以及血清生化变化。有趣的是,PPC治疗后,肝脏炎症水平、Th17/Treg细胞频率及相关细胞因子以及生化数据均有显著改变。

结论

这些发现表明,PPC在部分减轻NAFLD小鼠肝脏炎症反应中起关键作用,这涉及Treg/Th17细胞及其相关细胞因子的失衡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fed1/5483270/1e69f3c7bdc2/12865_2017_215_Fig1_HTML.jpg

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