MALT1在γδT细胞功能分化中的作用及其调控机制

项目名称： MALT1在γδT细胞功能分化中的作用及其调控机制

项目编号： No.31470872

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 高云飞

作者单位： 暨南大学

项目金额： 85万元

中文摘要： γδT细胞具有独特的生物学功能。但是，调控其功能分化的分子机制仍然不清楚。我们前期工作表明γδT细胞主要通过产生IFN-γ在肿瘤免疫中起着关键作用。MALT1在生理条件下与Bcl10和Carma共同组成CBM复合体，该复合体对T细胞的功能分化具有重要的调节作用。我们的初步工作显示：小鼠MALT1-/-γδT细胞被选择性地扩增，而其Th1分化显著地被抑制。本项目拟深入研究MALT1对γδ T细胞功能分化的调控机理。我们的科学问题是：1，MALT1基因在γδT细胞增殖和分化过程中究竟起着怎样的作用。2，其分子机制是什么? 3，MALT1对γδ T细胞介导的肿瘤免疫的影响是什么？阐明MALT1基因在γδT细胞功能分化中的作用，将有助于我们增强对γδT细胞的认识，同时为更好地将γδT细胞应用于肿瘤生物治疗奠定理论基础。

中文关键词： γδ；T细胞；细胞分化；细胞增殖；肿瘤免疫；NF-kB信号通路

英文摘要： γδT cells had unique biological functions. But, it is still not clear about the molecular mechanisms of how their differentiation and function were regulated. Our previous work showed that γδT cells play a key role in tumor immunity mainly through producing IFN-γ when activated.The gene of MALT1(mucosa‐ associated‐lymphoid‐tissue lymphoma‐translocation gene 1) was identified in lymphoma. Under physiological conditions, MALT1 together with Bcl10 and Carma are composed of CBM complex, which play an important role in regulating the differentiation and function of T cells. Our preliminary data showed that: mouse MALT1-/-γδ T cells could proliferate but their Th1 differentiation was inhibited dramatically. In this project, We are going to further investigate the mechanisms of how MALT1 regulate the function and differentiation of γδT cells. Based on these data, our scientific questions are: 1.How do MALT1 regulate the proliferation and differentiation of γδ T cells? 2.What's the mechanisms? 3.What's the effect of MALT1 on tumor immunity mediated by γδT cells? Ascertaining the function of MALT1 in regulating the differentiation and proliferation of γδ T cells will shed light on the biological functions of γδT cells, and provide the theoretical support for applying γδT cells to the biological therapy of tumors.

英文关键词： γδT cell;cell differentiation;cell proliferation;tumor immunity;NF-kB signaling