Significance of the balance between regulatory T (Treg) and T helper 17 (Th17) cells during hepatitis B virus related liver fibrosis.
Significance of the balance between regulatory T (Treg) and T helper 17 (Th17) cells during hepatitis B virus related liver fibrosis.
复制标题
乙型肝炎病毒相关肝纤维化期间调节性 T (Treg) 和辅助 T 17 (Th17) 细胞之间平衡的意义。
DOI：
10.1371/journal.pone.0039307
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Jiang W
中科院分区：
文献类型：
--
作者：
Li J;Qiu SJ;She WM;Wang FP;Gao H;Li L;Tu CT;Wang JY;Shen XZ;Jiang W
乙型肝炎病毒相关性肝纤维化（HBV-LF）通常由炎症发展为纤维化。然而，这两种病理状况之间的关系尚不完全清楚。本文假设调节性T （Treg）细胞和辅助性T 17 （Th17）细胞之间的平衡作为炎症指标可能预测HBV-LF的纤维化进展。采用流式细胞术检测77例hbeag阳性慢性乙型肝炎（CHB）患者和30例健康对照者的外周血Treg和Th17细胞的频率和表型。在CHB外周患者中，Treg和Th17频率均显著升高且相关，较低的Treg/Th17比值总是表明肝损伤和纤维化进展较多。为了研究Treg和Th17细胞在HBV-LF中的确切作用，我们使用来自外周的纯化CD4+、CD4+CD25+或CD4+CD25−细胞、从健康肝脏标本中分离的原代人肝星状细胞（hsc）、人重组白细胞介素(IL)-17细胞因子、抗IL-17抗体和HBcAg进行了一系列体外实验。在HBcAg的作用下，CD4+CD25+细胞以细胞接触和剂量依赖的方式显著抑制CD4+CD25 -细胞的增殖和细胞因子（尤其是IL-17和IL-22）的产生。此外，与HC患者相比，CHB患者的CD4+细胞显著促进人造血干细胞的增殖和活化。此外，CHB患者的CD4+CD25+细胞以显著的剂量依赖性方式抑制造血干细胞的增殖和活化，而重组IL-17反应促进造血干细胞的增殖和活化。最后，通过CD25+或IL-17+细胞的缺失，在豆豆蛋白a诱导的小鼠纤维化模型中获得了肝纤维化过程中Treg/Th17平衡影响的体内证据，观察到CD25缺失促进了肝损伤和纤维化进展，而IL-17缺失则减轻了肝损伤和纤维化进展。Treg/Th17平衡可能通过增加肝损伤和促进hsc激活来影响HBV-LF的纤维化进展。
Hepatitis B virus-related liver fibrosis (HBV-LF) always progresses from inflammation to fibrosis. However, the relationship between these two pathological conditions is not fully understood. Here, it is postulated that the balance between regulatory T (Treg) cells and T helper 17 (Th17) cells as an indicator of inflammation may predict fibrosis progression of HBV-LF. The frequencies and phenotypes of peripheral Treg and Th17 cells of seventy-seven HBeAg-positive chronic hepatitis B (CHB) patients who underwent liver biopsies and thirty healthy controls were determined by flow cytometry. In the periphery of CHB patients, both Treg and Th17 frequencies were significantly increased and correlated, and a lower Treg/Th17 ratio always indicated more liver injury and fibrosis progression. To investigate exact effects of Treg and Th17 cells during HBV-LF, a series of in vitro experiments were performed using purified CD4+, CD4+CD25+, or CD4+CD25− cells from the periphery, primary human hepatic stellate cells (HSCs) isolated from healthy liver specimens, human recombinant interleukin (IL)-17 cytokine, anti-IL-17 antibody and HBcAg. In response to HBcAg, CD4+CD25+ cells significantly inhibited cell proliferation and cytokine production (especially IL-17 and IL-22) by CD4+CD25− cells in cell-contact and dose-dependent manners. In addition, CD4+ cells from CHB patients, compared to those from HC subjects, dramatically promoted proliferation and activation of human HSCs. Moreover, in a dramatically dose-dependent manner, CD4+CD25+ cells from CHB patients inhibited, whereas recombinant IL-17 response promoted the proliferation and activation of HSCs. Finally, in vivo evidence about effects of Treg/Th17 balance during liver fibrosis was obtained in concanavalin A-induced mouse fibrosis models via depletion of CD25+ or IL-17+ cells, and it’s observed that CD25 depletion promoted, whereas IL-17 depletion, alleviated liver injury and fibrosis progression. The Treg/Th17 balance might influence fibrosis progression in HBV-LF via increase of liver injury and promotion of HSCs activation.
登录
查看更多内容
DOI：
10.1084/jem.193.11.1303
发表时间：
2001-06-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dieckmann D;Plottner H;Berchtold S;Berger T;Schuler G
通讯作者：
Schuler G
影响因子：
4.8
作者：
Liu, CH;Gaça, MDA;Wells, RG
通讯作者：
Wells, RG
影响因子：
13.5
作者：
Stoop, JN;van der Molen, RG;Janssen, HLA
通讯作者：
Janssen, HLA
影响因子：
32.4
作者：
Winau, Florian;Hegasy, Guido;Kaufmann, Stefan H. E.
通讯作者：
Kaufmann, Stefan H. E.
影响因子：
100.3
作者：
Weaver, Casey T.;Hatton, Robin D.
通讯作者：
Hatton, Robin D.