新型免疫负调控分子TIPE2调控CD4+T细胞的功能及在HBV感染中的作用研究

肿瘤坏死因子α诱导蛋白8样分子2（Tumor necrosis factor-α induced protein 8 like 2, TIPE2） 是新发现的一个重要免疫负调控分子，具有调节宿主免疫和适应性免疫的作用。我们前期研究表明慢性HBV感染存在免疫紊乱，TIPE2可能参与了CD4+辅助性T细胞的调控，但其机制未明。我们提出如下科学假设：① TIPE2基因可以调节HBV感染Th细胞亚群的分化；②NF-kB通路可能是TIPE2调控Th细胞分化的有效信号转导途径。为论证上述科学问题，本研究从临床、细胞模型和动物模型三个方面，运用基因敲除小鼠、细胞转染、RNA干扰、信号转导和免疫学技术，研究TIPE2在HBV感染中对Th细胞分化功能的调节作用和分子机制，对深入揭示乙型肝炎的免疫机制、寻找新型免疫治疗靶点具有重要的理论意义和应用价值。

Tumor necrosis factor-α induced protein 8 like 2(TIPE2) is a newly identified negative immune regulatory molecular with the capacity of modulating innate and adaptive immune response. We previously demonstrated the imbalance of T helper immune response in HBV infection and TIPE2 might take a role in this progression. Thus we hypothesis that: ① TIPE2 gene can modulate exactly the Th cell differentiation under HBV infection;② NF-kB might be a central signaling pathway in the Th cell differentiation stimulated by TIPE2. Herein, clinical blood and liver donor samples, cell lines and knockout mice would be used for determination, to explore the possible mechanism of TIPE2 in modulating the Th cell differentiation under HBV infection. This present proposal would be essential for the pathogenesis of hepatitis b and targeted immune therapy.