Activated hepatic stellate cells directly induce pathogenic Th17 cells in chronic hepatitis B virus infection
Activated hepatic stellate cells directly induce pathogenic Th17 cells in chronic hepatitis B virus infection
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慢性乙型肝炎病毒感染中激活的肝星状细胞直接诱导致病性Th17细胞
DOI：
10.1016/j.yexcr.2017.08.001
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发表时间：
2017-10
影响因子：
3.7
通讯作者：
Wei Jiang
中科院分区：
文献类型：
--
作者：
Yun Liu;Lei Li;Jiang Liu;Weimin She;Jiemin Shi;Jing Li;Jiyao Wang;Wei Jiang
Th17细胞通过激活肝星状细胞(HSCs)参与肝纤维化。我们的目的是研究HSCs是否能够调节Th17细胞的功能，并确定相关的机制。65例慢性乙型肝炎(CHB)患者入选本研究。为探讨HSCs对T细胞的影响，从CHB患者体内分选原始的CD4+T细胞和Th17细胞，加入或不加入活化的HSCs进行培养，分析细胞因子的表达和基因转录。此外，还对HSCs的调控机制进行了探讨。在IL-17A、IL-23R、RORC、CCL20和CCR6表达的基础上，ELISA和qRT-PCR显示CHB患者的Th17细胞具有更强的致病性，同时它们也能激活原代HSC。共培养实验表明，活化的HSCs以时间和剂量依赖的方式显著促进了CD4+T细胞的增殖。此外，它们还可以诱导幼稚的CD4+T细胞成为具有更多致病表型的Th17细胞。此外，活化的HSC介导的Th17细胞的诱导可能依赖于IL-1β和IL-6的释放以及COX-PGE_2途径。Th17细胞与HSCs在促炎反馈环中的协同作用可能有助于更好地理解Th17细胞在慢性乙肝感染中的致病作用。
Th17 cells are involved in liver fibrosis by activating hepatic stellate cells (HSCs). We aimed to investigate whether HSCs are able to regulate the function of Th17 cells and to determine the relevant mechanism. Sixty-five patients diagnosed with chronic hepatitis B (CHB) were enrolled in this study. To determine the effect of HSCs on T cells, naïve CD4+T cells and Th17 cells were sorted from CHB patients and cultured with or without activated-HSCs, and cytokine expression and gene transcription were analyzed. In addition, the regulatory mechanism of HSCs was investigated. ELISA and qRT-PCR showed that Th17 cells from CHB patients were more pathogenic, on the basis of the expression of IL-17A, IL-23R, RORC, CCL20 and CCR6, and meanwhile, they could activate the primary HSCs. Co-culture experiments indicated that activated HSCs dramatically promoted proliferation of CD4+T cells in a time- and dose-dependent manner. In addition, they could induce naïve CD4+T cells to become Th17 cells which had a more pathogenic phenotype. Moreover, activated HSCs-mediated induction of Th17 cells might depend on the release of IL-1β and IL-6 as well as on the COX-PGE2 pathway. Th17 cells cooperated with HSCs in a proinflammatory feedback loop might provide a better understanding of the pathogenic role of Th17 cells in the chronicity of HBV infection.
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影响因子：
7
作者：
Florian Winau;C. Quack;Alexandre Darmoise;S. Kaufmann
通讯作者：
Florian Winau;C. Quack;Alexandre Darmoise;S. Kaufmann
DOI：
10.3410/f.715697903.793302834
发表时间：
2012-07
期刊：
--
影响因子：
--
作者：
D. Moody;A. Jong
通讯作者：
D. Moody;A. Jong
影响因子：
82.9
作者：
Yao, Chengcan;Sakata, Daiji;Narumiya, Shuh
通讯作者：
Narumiya, Shuh
影响因子：
13.5
作者：
Yu, MC;Chen, CH;Qian, SG
通讯作者：
Qian, SG
DOI：
--
发表时间：
2004-07
期刊：
The Journal of rheumatology
影响因子：
--
作者：
L. Stamp;L. Cleland;M. James
通讯作者：
L. Stamp;L. Cleland;M. James