人黏膜组织中IFN-γ/IL-21共表达CD4+ T细胞的作用和可塑性研究

项目名称： 人黏膜组织中IFN-γ/IL-21共表达CD4+ T细胞的作用和可塑性研究

项目编号： No.31470888

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： 吴长有

作者单位： 中山大学

项目金额： 97万元

中文摘要： 传统观点认为不同的Th细胞亚群表达特定的细胞因子和转录因子，发挥不同的免疫功能。我们的研究发现，炎症性黏膜组织中的Th细胞与淋巴结和周围血中的不同，有较高比例的CD4+ T细胞共表达IFN-γ/IL-21，具有Th1和Tfh细胞的共有特征。目前仍不确定这些共表达IFN-γ/IL-21的CD4+ T细胞是如何分化而来？进一步的分化方向及功能如何？本项目拟在原有的工作基础上，对IFN-γ+IL-21+CD4+ T细胞的功能和可塑性进行研究：①IFN-γ+IL-21+CD4+ T细胞与Th1细胞和Tfh细胞在细胞因子、转录因子和表型之间的差异以及相互转化关系；②诱导IFN-γ+IL-21+CD4+ T细胞分化的条件；③在炎性黏膜疾病中IFN-γ+IL-21+CD4+ T细胞的作用。该研究将揭示Th1-Tfh样细胞的表型、分化以及功能特点，为阐明炎性黏膜疾病的发生、发展以及治疗提供新的理论依据。

中文关键词： 黏膜免疫；CD4+；T细胞；细胞分化

英文摘要： Traditional views suggested that CD4+ T helper cells expressed specified cytokines and transcriptional factors, play important immune function in immunologic process. Our previously studies showed that Th cells of inflammatory mucosal tissues were different with that of lymph node and peripheral blood. Inflammatory mucosal tissues contained high level of IFN-γ/IL-21 coexpressing CD4+ T cells, which share features of both Tfh and Th1 cells. It's still unclear that how do these CD4+IFN-γ+ IL-21+ T cells differentiate? Are these cells a new cells subset or just transitional state in cell differentiation? What about the function and the further differentiation? Our project intends to explore following issues: ① the difference of cytokines, transcriptional factors and phenotype of CD4+IFN-γ+ IL-21+ T cells with that of Th1 cells or Tfh cells in inflammatory mucosal tissues, the conversion relationship between CD4+IFN-γ+ IL-21+ T cells and Tfh or Th1; ② the condition that induce the differentiation of CD4+IFN-γ+ IL-21+ T cells; ③ the function of CD4+IFN-γ+ IL-21+ T cells in inflammatory mucosal tissues. Our aim is to understand the cellular phenotype, differentiation and function of Th1-Tfh like cells. We hope that our work may provide theoretical basis for the control of inflammatory mucosal diseases.

英文关键词： mucosal immunity;CD4+ T cells;cell differentiation