miR-146a介导HCV感染者单核细胞Toll样受体4天然免疫应答耐受的作用探讨

项目名称： miR-146a介导HCV感染者单核细胞Toll样受体4天然免疫应答耐受的作用探讨

项目编号： No.81202321

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学免疫学、法医学

项目作者： 彭程

作者单位： 华中科技大学

项目金额： 23万元

中文摘要： 丙型肝炎病毒(HCV)对宿主天然免疫系统的破坏是造成HCV逃逸免疫监视的主要原因之一。miR-146a是单核细胞Toll样受体4(TLR4)通路重要的负性调节因子，前期研究发现HCV慢性感染者来源的外周血单核细胞TLR4信号通路反应低下,HCV感染者外周血单核细胞中miR-146a表达显著升高，提示miR-146a可能参与HCV感染所致单核细胞TLR4通路免疫应答耐受。本项目拟用病毒转染、RNA干扰等方法研究HCV病毒蛋白对单核细胞miR-146a表达的影响，并分别运用转染HCV core蛋白的单核细胞系和患者来源的单核细胞两种培养体系，明确miR-146a对HCV感染者单核细胞功能和TLR4信号通路的效应及机制，探讨针对miR-146a靶向调节恢复HCV感染者单核细胞免疫功能的可能性，为进一步探索新的HCV免疫治疗方法提供实验基础。

中文关键词： 丙型肝炎病毒（HCV）；单核细胞；微小RNA；Toll样受体；

英文摘要： To suppress the host immune system is one of the ways for HCV escaping immune surveillance. MiR-146a acts as a critical negatative regulator of TLR4 pathway. Monocytes from chronic HCV-infected patients had impaired response in TLR4 signaling pathway. Our preliminary study indicated that the expression of miR-146a in peripheral monocytes was significantly increased in patients with HCV infection, suggesting that miR-146a may be involved in the dysfunction of TLR4 pathway of monocytes from HCV-infected patients. In this study, we plan to apply viral transfection, RNA interference and some other methods to investigate the effects of HCV on miR-146a expression. In addition, the monocytes with HCV core transfection and those from HCV-infected patients will be used to study the roles of miR-146a on the function of HCV-infected monocytes and TLR4 pathway.Therefore, this project may help to elucidate the function of miR-146a in HCV infection-inducing immune tolerance in TLR4 pathway and to explore the possibility of restoring immune function of monocytes from HCV-infected patients by targeted inhibition of miR-146a，providing basis for developing new immune therapy methods against HCV infection in the future.

英文关键词： HCV；monocytes；microRNA；Toll like receptor(TLR)；