树突状细胞中TGF-β/Smad3通路相关miRNA参与天然免疫调控的作用及其机制研究

项目名称： 树突状细胞中TGF-β/Smad3通路相关miRNA参与天然免疫调控的作用及其机制研究

项目编号： No.31470849

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： 苏小平

作者单位： 中国人民解放军第二军医大学

项目金额： 85万元

中文摘要： 正在世界各地肆虐的禽流感引起全世界包括中国科学家对天然免疫的关注，天然免疫反应的精密调控对机体至关重要，树突状细胞在天然免疫反应的精密调控中扮演了关键的角色。以往的研究注重信号通路在转录水平对炎性因子表达的调控，而我所的研究表明信号通路还可以通过miRNA在转录后水平影响炎性因子的表达，故我们推测树突状细胞通过miRNA广泛参与天然免疫反应的精密调控，但是其具体机制还不清楚。作者前期的研究表明树突状细胞中TGF-β/Smad3通路通过miR-30b参与天然免疫的负向调控，故本研究拟对树突状细胞中涉及TGF-β/Smad3通路的miRNA进行全面的探索，进而研究这些miRNA参与天然免疫调控的作用及其机制。通过以上研究我们将明确树突状细胞中TGF-β/Smad3通路相关的miRNA参与天然免疫调控的作用及其机制。本研究将为天然免疫相关疾病的诊治提供新的靶点和理论基础。

中文关键词： 天然免疫；树突状细胞；微小RNA；TGF-β/Smad通路；免疫调控

英文摘要： The innate immune system is the first defense line against pathogen infection in multicellular organism. Innate immune activation must be regulated carefully, so as not to cause excessive inflammation and immune injury. Dendritic cells plays an important role in the innate immune response. Previous studies focus on the signaling pathway in the transcriptional regulation of coding gene such as inflammatory factor in dendritic cells. Our research shows that signal pathway TGF-β/Smad3 can also regulate the expression of miR-30b, and then influence the expression of inflammatory cytokines. So we hypothesis that signal transduction pathway can regulate the expression of miRNAs to participate in innate immune response. We have obtained the whole miRNome of dendritic cells in differentiation and maturation processes. So in this study, we select the key signaling pathway in dendritic cells to investigate the role and molecular mechanism of special miRNA on the effection of inflammatory factors. We first identified the miRNAs which changes significantly with the selected pathway, and then investigate these their regulation in natural immunity. Through this study, we will clear the and mechanism of signal transduction pathway in innate inflammatory through miRNA. This study will further define the regulation and molecular mechanism of signal transduction pathway in innate immunity.

英文关键词： Innate immunity;Dendritic cells;miRNA;TGF-β/Smad3 pathway;Immune regulation