项目名称: IL-35介导的肠道B细胞与调节性T细胞协同缓解炎症性肠病的机制研究
项目编号: No.81501394
项目类型: 青年科学基金项目
立项/批准年度: 2016
项目学科: 医药、卫生
项目作者: 汪路曼
作者单位: 复旦大学
项目金额: 18万元
中文摘要: 炎症性肠病是一种慢性黏膜免疫相关疾病,其发病机制尚不明确。我们前期研究发现肠道局部B细胞与调节性T细胞通过协同作用,对IBD的缓解至关重要;且在这一相互作用过程中,肠粘膜B细胞大量分泌抑制性免疫分子IL-35。过表达B细胞来源的IL-35,Treg增殖明显,疾病缓解。因此我们推测IL-35介导了B-Treg间的相互作用,维护了肠道的免疫平衡。因此,本项目拟在前期基础上,通过IBD小鼠模型,以局部肠相关淋巴细胞中的免疫细胞和分子为研究对象,借助基因敲除技术、免疫细胞分选和动态成像等技术深入探讨:在IBD微环境中,B细胞来源的IL-35是否在促进Treg细胞增殖中起到关键作用;以及B细胞分泌的IL-35及其受体在促进Treg增殖的过程中的关键分子通路及机制。本研究提出IL-35/IL-35R轴介导的B细胞和Treg之间的对话是缓解IBD的新作用机制,为进一步临床干预IBD提供了新靶点。
中文关键词: 自身免疫性;自身免疫调节因子
英文摘要: Inflammation Bowel Disease is a chronic mucosal immune disease, the pathogenesis of IBD remains poorly understood. On our previous study, we demonstrated that gut B cells and Tregs cooperate to form a regulatory loop that maintains gut homeostasis and suppresses IBD. Moreover, B Cells secreted regulatory cytokine IL-35. Treg proliferated and disease alleviated when over expression of B cell derived IL-35. Thus, we predict that IL-35 mediated gut B cell and Treg cell cooperation in suppressing colitis. In this project, we are going to use colitis murine model, analyze mucosal immune cell and molecular by technologies such as cell sorting and dynamic imaging, intend to clarify: In IBD microenvironment, whether B cells derived IL-35 play a key role in promote the proliferation of Treg? And find IL-35 receptors and the signaling pathway of IL-35 receptors by which Treg proliferation. These findings may explore that IL-35/IL-35R mediated immune response is new mechanisms of B cell and Treg interaction in rescue IBD and provide new insights for therapeutic approaches in IBD.
英文关键词: autoimmune;regulatory cytokine