Faecalibacterium prausnitzii协同LFA-1在炎症性肠病发生中调控淋巴细胞分化及功能的作用机制

项目名称： Faecalibacterium prausnitzii协同LFA-1在炎症性肠病发生中调控淋巴细胞分化及功能的作用机制

项目编号： No.81470819

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 于成功

作者单位： 南京大学

项目金额： 73万元

中文摘要： 肠道菌群紊乱引起的免疫应答异常在IBD的发生中起重要作用，而肠道普拉梭菌（F. pransnitzii）减少是IBD肠道菌群紊乱的重要特征。我们前期研究发现，F. prausnitzii和淋巴细胞功能抗原-1（LFA-1）参与了淋巴细胞的分化和功能调节，但二者内在关联的协同效应和机制尚不清楚。本课题以LFA-1基因缺失鼠及IBD患者为研究对象，通过DSS诱导IBD模型观察F. prausnitzii及LFA-1与IBD发生的关系；通过检测外周血、肠粘膜及肠系膜淋巴结等组织内CD4+T细胞亚群数量及相关TLR相关调节蛋白和效应细胞因子的变化；分析F. pransnitzii、LFA-1调控CD4+T细胞分化特征及与IBD临床病理表型的关系；同时通过体外干预T细胞的分化与功能分析，探讨F. prausnitzii与LFA-1调控淋巴细胞分化的协同作用关系及机制，为IBD的治疗干预提供新的策略。

中文关键词： 炎症性肠病；普拉梭菌；肠道菌群；淋巴细胞功能抗原；T细胞

英文摘要： The inappropriate immune response to gut microbiota plays a key role in the development of inflammatory bowel disease(IBD). An important feature of gut dysbiosis in IBD patients is the decreasing of Faecalibacterium prausnitzii(F. prausnitzii). Our previous study results indicated that F. prausnitzii and lymphocyte function associated antigen-1(LFA-1) may be involved in the differentiation and function regulation of lymphocytes, but the cooperative effects and mechanism of F. prausnitzii and LFA-1 is still unclear. The study will be performed in patients with IBD and animal model with LFA-1 gene knockout mice induced by DSS to observe the relationship between IBD with F. prausnitzii and LFA-1. The subsets of CD4+ T lymphocytes and the realted protein of Toll-like receptors as well as cytokines will be detected in peripheral blood and lmphatic tissues in intstinal mucosa and mesenteric lymph nodes for investigating the effects of F. prausnitzii and LFA-1 on the CD4+ T lymphocyte differentiation and their relationship with clinicopathologic phenotypes. The intervention study in vitro on the differentiation and funtion regulation of T lymphocytes will be performed to illuminate the cooperative effects and mechanism of F. prausnitzii and LFA-1. The study results should be utilized to help to develop therapeutic strategies for IBD.

英文关键词： Inflammatory bowel disease;Faecalibacterium prausnitzii;Gut microbiota;Lymphocyte function associated antigen;T lymphocyte