巨噬细胞活化导致的肠黏膜屏障功能障碍是IBD的重要机制之一。外泌体是细胞分泌的微小囊泡，近来被发现可作为信号分子在细胞间行使信息交流功能。本课题组长期研究肠黏膜上皮细胞之间的相互作用，前期结果发现：活化的巨噬细胞可介导IBD肠黏膜屏障功能障碍；巨噬细胞活化释放外泌体的数量明显增加；经芯片分析发现外泌体内多种miRNA上调，以miR-223最为显著。据此推测:巨噬细胞活化后通过分泌外泌体，传递miR-223，调控肠黏膜屏障，影响IBD的发生发展。在本研究中，拟证实巨噬细胞在活化后可分泌富含miR-233的外泌体，验证miR-223对肠黏膜屏障功能和微生态的影响，寻找miR-223通过何种下游靶蛋白影响肠黏膜屏障功能，并在IBD患者肠道组织样本中验证miR-223与IBD的关系。本课题有望发现外泌体miR-223在IBD中的重要作用，并为IBD发生发展机制的探索及治疗途径提供新的实验依据。

It is widely acknowledged that the impairment of intestinal barrier induced by the activated macrophages serves as one of the important mechanisms for the onset of IBD. Exsomes, small membrane vesicles, are commonly regarded as a new vehicle that transports genetic material between cells. Our previous studies mainly focused on the exploration of interaction of intestinal epithelial cells and we found that activated macrophages caused the dysfunction of intestinal barrier and secretion of an aberrantly elevated level of exsomes. We also demonstrated that various miRNAs were overexpressed in those exosomes through chip, among which miR-223 was observed with the largest accumulation. Based on those data, we raised a hypothesis that activated macrophages could secrete exosomes transporting miR-223 to the intestinal epithelial cells, which might regulate the function of intestinal barrier during the pathogenesis and progression of IBD. In this study, we aimed to detect whether activated macrophages could secrete exosomes transporting miR-223 to intestinal epithelial cells and explore how miR-223 impacted the intestinal barrier and microbiota. Besides, the signaling pathways and targeted proteins related to permeability would also be analyzed. Finally we will verify the relations between miR-223 and IBD in biopsy tissues from IBD patients. We believe that this study would uncover the important role of exosomal miR-223 in IBD and provide theoretical basis for the investigation of specific mechanisms and development of potential therapeutic pathway against IBD.