DNA甲基化调控CD8+T细胞免疫反应在HBV感染中的作用和机制研究

CD8+T细胞免疫反应是HBV感染能否有效清除的关键环节，受多种因素调节。我们前期发现DNA甲基化参与了乙型肝炎的发生发展过程，与HBV病毒复制和免疫清除有关。在此基础上，我们认为DNA甲基化可能通过调控HBV特异性CD8+T细胞反应，参与HBV感染的免疫损伤及病毒清除过程。为验证这一假说，我们拟利用临床、细胞和HBV转基因小鼠模型等，采用分子生物学、免疫学和生物化学等多种方法，筛选HBV特异性CD8+T细胞免疫反应中的关键基因甲基化位点，研究关键基因DNA甲基化对HBV感染CD8+T淋巴细胞反应的调控作用，阐明DNA甲基化调控CD8+T淋巴细胞反应的分子机制，为清除乙型肝炎病毒提供新的潜在治疗靶点，对慢性乙型肝炎的治疗具有重要的理论和现实意义。

Hepatitis B virus (HBV) infection is a global health problem and HBV itself is able to alter the epeigenetic modifications of whole genemo DNA. We previsouly reported that multiple genes were characterised with methylaton in gene promoter locis during HBV stimulated liver injury and virus eradication. Furhtermore, we also reported clinical assocations between DNA methylation and HBeAg seroconversion in patients with chonric hepatitis B. Therefore, we hypothsize that DNA methylation might be core element for HBV specific CD8+T cytotoxic T cell response and onxidative stress in liver injury, and to anti-HBV activity during HBV infection. Our proposal aims to investigate how DNA methylation affect liver injury and viral eradication during HBV infection. The whole genemo DNA methylation, HBV speicific CD8+T cells, methylation for critical genes in T cell differeation, oxidative stress and viral replication would be studied in this propasl.Ideally, this proposal will provide considerable views of immune responses and new target to break immune tolerance in chornic hepatitis B.