HCV infection enhances Th17 commitment, which could affect the pathogenesis of autoimmune diseases.
HCV infection enhances Th17 commitment, which could affect the pathogenesis of autoimmune diseases.
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DOI：
10.1371/journal.pone.0098521
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Shimosegawa T
中科院分区：
文献类型：
--
作者：
Kondo Y;Ninomiya M;Kimura O;Machida K;Funayama R;Nagashima T;Kobayashi K;Kakazu E;Kato T;Nakayama K;Lai MM;Shimosegawa T
各种自身免疫性疾病的发生与丙型肝炎病毒持续感染和Th17细胞密切相关。以前，本课题组报道，除了诱导免疫球蛋白高突变外，T淋巴细胞中丙型肝炎病毒的存在还可能影响CD4+辅助T细胞的发育和增殖。因此，我们分析了丙型肝炎病毒持续感染与体内外Th17细胞诱导机制的关系。慢性丙型肝炎患者(CH-C)自身免疫相关疾病的患病率明显高于其他类型的慢性肝炎(乙肝和非酒精性肝炎)。慢性丙型肝炎患者IL-6和转化生长因子-β双高的发生率明显高于其他肝病。此外，这些双高患者的抗核抗体、冷球蛋白血症和嗜淋巴丙型肝炎病毒阳性率显著高于对照组，且IL-1-β、IL-21、IL-23水平也较高。除了先前报道的嗜淋巴-丙型肝炎病毒株外，我们还通过深度测序分析发现了一种新的1b型嗜淋巴丙型肝炎病毒(Ly-HCV)。在IL-1β、IL-23、IL-6和转化生长因子-β等多种细胞因子作用下，体外培养的淋巴样细胞中均可检测到嗜淋性丙型肝炎病毒复制。丙型肝炎病毒感染可显著促进Th17细胞的发育。丙型肝炎病毒核心蛋白为丙型肝炎病毒核心蛋白，可增强STAT-3信号转导，上调rORγt作为Th17主控基因的表达。嗜淋性丙型肝炎病毒感染可能促进Th17的发育，有助于了解自身免疫相关疾病的发病机制。
Various kinds of autoimmune diseases have been reported to have a significant relationship with persistent hepatitis c virus (HCV) infection and Th17 cells. Previously, our group reported that the existence of HCV in T lymphocytes could affect the development of CD4+ helper T cells and their proliferation, in addition to the induction of immunoglobulin hyper-mutation. Therefore, we analyzed the relationship between persistent infection of HCV and the mechanism of Th17 cell induction ex vivo and in vitro. The prevalence of autoimmune-related diseases in chronic hepatitis c patients (CH-C) was significantly higher than in other types of chronic hepatitis (hepatitis B and NASH). A significantly higher frequency of IL6 and TGF-β double-high patients was detected in CH-C than in other liver diseases. Moreover, these double-high patients had significantly higher positivity of anti-nuclear antibody, cryoglobulinemia, and lymphotropic HCV and higher amounts of IL1-β, IL21, IL23. In addition to the previously reported lymphotropic SB-HCV strain, we found a novel, genotype 1b lymphotropic HCV (Ly-HCV), by deep sequencing analysis. Lymphotropic-HCV replication could be detected in the lymphoid cells with various kinds of cytokine-conditions including IL1β, IL23, IL6 and TGF-β in vitro. Infection by HCV could significantly enhance the development of Th17 cells. The HCV protein responsible for inducing the Th17 cells was HCV-Core protein, which could enhance the STAT-3 signaling and up-regulate the expression of RORγt as a Th17 master gene. Infection by lymphotropic HCV might enhance the Th17 development and contribute to understanding the pathogenesis of autoimmune-related diseases.
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