CD4(+) T cell activation and inflammation in NASH-related fibrosis.
CD4(+) T cell activation and inflammation in NASH-related fibrosis.
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DOI：
10.3389/fimmu.2022.967410
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发表时间：
2022
影响因子：
7.3
通讯作者：
Zheng, Feng
中科院分区：
文献类型：
--
作者：
Zhou, Yunfeng;Zhang, Haibo;Yao, Yao;Zhang, Xiaoyan;Guan, Youfei;Zheng, Feng
肝纤维化是终末期肝衰竭的常见病理特征，终末期肝衰竭是一种严重危及生命的疾病。非酒精性脂肪性肝病（NAFLD），特别是其更严重的形式与脂肪性肝炎（NASH），由肥胖，2型糖尿病和代谢综合征引起，并成为肝纤维化的主要原因。遗传因素、脂质过负荷/毒性、氧化应激和炎症都与NASH的发生和进展有关。先天性免疫应答和适应性免疫都有助于NASH相关炎症。先天性免疫可通过炎症相关分子模式引起炎症和随后的纤维化。越来越多的证据表明，T细胞介导的适应性免疫也通过细胞毒性、细胞因子和其他促炎和促纤维化介质引起NASH中的炎症和纤维化。最近，单细胞转录组分析已经揭示，CD 4 + T细胞、CD 8 + T细胞、γδ T细胞和TEM的群体在患有NASH的肝脏中扩增。T细胞的活化需要来自专职抗原呈递细胞（APC）的抗原呈递，包括巨噬细胞、树突状细胞和B细胞。然而，由于肝细胞表达MHCII分子和共刺激因子，它们也可以作为非典型APC来促进T细胞活化。此外，NASH中肝细胞向促炎细胞的表型转换有助于炎症的发展。在这篇综述中，我们重点关注T细胞，特别是CD 4 + T细胞，并讨论了不同的CD 4 + T细胞亚群，包括Th 1，Th 2，Th 17，Th 22和Treg在NASH相关的肝脏炎症和纤维化中的作用。
Liver fibrosis is a common pathological feature of end stage liver failure, a severe life-threatening disease worldwide. Nonalcoholic fatty liver disease (NAFLD), especially its more severe form with steatohepatitis (NASH), results from obesity, type 2 diabetes and metabolic syndrome and becomes a leading cause of liver fibrosis. Genetic factor, lipid overload/toxicity, oxidative stress and inflammation have all been implicated in the development and progression of NASH. Both innate immune response and adaptive immunity contribute to NASH-associated inflammation. Innate immunity may cause inflammation and subsequently fibrosis via danger-associated molecular patterns. Increasing evidence indicates that T cell-mediated adaptive immunity also provokes inflammation and fibrosis in NASH via cytotoxicity, cytokines and other proinflammatory and profibrotic mediators. Recently, the single-cell transcriptome profiling has revealed that the populations of CD4+ T cells, CD8+ T cells, γδ T cells, and TEMs are expanded in the liver with NASH. The activation of T cells requires antigen presentation from professional antigen-presenting cells (APCs), including macrophages, dendritic cells, and B-cells. However, since hepatocytes express MHCII molecules and costimulators, they may also act as an atypical APC to promote T cell activation. Additionally, the phenotypic switch of hepatocytes to proinflammatory cells in NASH contributes to the development of inflammation. In this review, we focus on T cells and in particular CD4+ T cells and discuss the role of different subsets of CD4+ T cells including Th1, Th2, Th17, Th22, and Treg in NASH-related liver inflammation and fibrosis.
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DOI：
10.1111/dom.14322
发表时间：
2021-05
期刊：
Diabetes, obesity & metabolism
影响因子：
--
作者：
Cariou B;Byrne CD;Loomba R;Sanyal AJ
通讯作者：
Sanyal AJ
T细胞共刺激和共抑制的分子机制。
DOI：
10.1038/nri3405
发表时间：
2013-04
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
25.7
作者：
Gaul S;Leszczynska A;Alegre F;Kaufmann B;Johnson CD;Adams LA;Wree A;Damm G;Seehofer D;Calvente CJ;Povero D;Kisseleva T;Eguchi A;McGeough MD;Hoffman HM;Pelegrin P;Laufs U;Feldstein AE
通讯作者：
Feldstein AE
影响因子：
5.8
作者：
Dixon LJ;Barnes M;Tang H;Pritchard MT;Nagy LE
通讯作者：
Nagy LE
影响因子：
8
作者：
Bieghs, Veerle;Trautwein, Christian
通讯作者：
Trautwein, Christian