Hepatitis B virus induces IL-23 production in antigen presenting cells and causes liver damage via the IL-23/IL-17 axis.
Hepatitis B virus induces IL-23 production in antigen presenting cells and causes liver damage via the IL-23/IL-17 axis.
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乙型肝炎病毒诱导抗原呈递细胞产生 IL-23，并通过 IL-23/IL-17 轴引起肝损伤
DOI：
10.1371/journal.ppat.1003410
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发表时间：
2013
期刊：
影响因子：
6.7
通讯作者：
Wu Y
中科院分区：
文献类型：
--
作者：
Wang Q;Zhou J;Zhang B;Tian Z;Tang J;Zheng Y;Huang Z;Tian Y;Jia Z;Tang Y;van Velkinburgh JC;Mao Q;Bian X;Ping Y;Ni B;Wu Y
IL-23调节先天性和适应性免疫系统中的无数过程，并且是许多疾病中Th 17细胞发挥的促炎作用的关键介质。在这项研究中，我们调查了是否以及如何B型肝炎病毒（HBV）直接通过IL-23信号通路引起肝损伤。在HBV感染患者的肝活检组织中，IL-23和IL-23 R的表达均显著升高。体内观察还表明，IL-23的主要来源是髓样树突状细胞（mDC）和巨噬细胞。从健康供体分离的体外分化的未成熟DC和巨噬细胞的分析显示，HBV表面抗原（HBsAg）以甘露糖受体（MR）依赖性方式有效地诱导IL-23分泌。用内体酸化抑制剂和发动蛋白抑制剂培养显示，在与MR结合后，HBsAg通过内吞机制被mDC和巨噬细胞摄取。相反，虽然HBV核心抗原（HBcAg）也可以刺激mDC分泌IL-23，但该过程不依赖于MR和内吞作用。此外，IL-23被证明是HBsAg刺激的幼稚CD 4 + T细胞分化为Th 17细胞所必需的，Th 17细胞被确定为HBV感染肝脏中IL-17的主要来源。肝星状细胞和mDC上存在IL-17受体，可能是IL-17在B型肝炎中的潜在靶细胞。这些数据为HBV诱导的肝炎的尚未认识的机制提供了新的见解，通过该机制，IL-23表达的增加，通过MR/内吞依赖性或非依赖性方式，通过IL-23/IL-17轴产生肝损伤。
IL-23 regulates myriad processes in the innate and adaptive immune systems, and is a critical mediator of the proinflammatory effects exerted by Th17 cells in many diseases. In this study, we investigated whether and how hepatitis B virus (HBV) causes liver damage directly through the IL-23 signaling pathway. In biopsied liver tissues from HBV-infected patients, expression of both IL-23 and IL-23R was remarkably elevated. In vivo observations also indicated that the main sources of IL-23 were myeloid dendritic cells (mDCs) and macrophages. Analysis of in vitro differentiated immature DCs and macrophages isolated from healthy donors revealed that the HBV surface antigen (HBsAg) efficiently induces IL-23 secretion in a mannose receptor (MR)-dependent manner. Culture with an endosomal acidification inhibitor and the dynamin inhibitor showed that, upon binding to the MR, the HBsAg is taken up by mDCs and macrophages through an endocytosis mechanism. In contrast, although the HBV core antigen (HBcAg) can also stimulate IL-23 secretion from mDCs, the process was MR- and endocytosis-independent. In addition, IL-23 was shown to be indispensible for HBsAg-stimulated differentiation of naïve CD4+ T cells into Th17 cells, which were determined to be the primary source of IL-17 in HBV-infected livers. The cognate receptor, IL-17R, was found to exist on the hepatic stellate cells and mDCs, both of which might represent the potential target cells of IL-17 in hepatitis B disease. These data provide novel insights into a yet unrecognized mechanism of HBV-induced hepatitis, by which increases in IL-23 expression, through an MR/endocytosis-dependent or -independent manner, produce liver damage through the IL-23/IL-17 axis.
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影响因子：
5.4
作者：
Gu, Yongpeng;Yang, Jianfei;Ouyang, Xinshou;Liu, Weicheng;Li, Hongxing;Yang, Jianjun;Bromberg, Jonathan;Chen, Shu-Hsia;Mayer, Lloyd;Unkeless, Jay C.;Xiong, Huabao
通讯作者：
Xiong, Huabao
DOI：
10.4049/jimmunol.0803683
发表时间：
2009-06-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Lee BO;Tucker A;Frelin L;Sallberg M;Jones J;Peters C;Hughes J;Whitacre D;Darsow B;Peterson DL;Milich DR
通讯作者：
Milich DR
影响因子：
4.8
作者：
Aggarwal, S;Ghilardi, N;Gurney, AL
通讯作者：
Gurney, AL
影响因子：
5.4
作者：
Drummond, Rebecca A.;Saijo, Shinobu;Iwakura, Yoichiro;Brown, Gordon D.
通讯作者：
Brown, Gordon D.
影响因子：
9.1
作者：
Ge, Jian;Wang, Kai;Fan, Yu-Chen
通讯作者：
Fan, Yu-Chen