脆弱拟杆菌上调ILC3/IL-22/pSTAT3通路促进炎症性肠病黏膜愈合的机制研究

肠道共生菌与黏膜上皮的相互作用不仅影响着炎症性肠病（IBD）的发生发展，还在IBD黏膜愈合中发挥重要作用。ILC3/IL-22/pSTAT3轴被认为是肠道共生菌介导黏膜修复的重要通路，但具体哪种细菌对其进行调控仍未阐明。前期工作中，我们发现长时间抗生素的应用会导致实验性肠炎黏膜修复延迟，而我们自主分离得到的脆弱拟杆菌却能逆转这一过程，且增加了肠道IL-22的表达。我们推测脆弱拟杆菌可能通过调控肠道菌群，直接或间接影响了ILC3/IL-22通路，进而介导肠上皮细胞的增殖迁移，促进IBD黏膜愈合。本项目拟构建小鼠肠炎模型，结合临床标本、转基因动物和体外实验，深入探讨共生菌与共生菌、共生菌与肠上皮互作影响肠黏膜愈合的调控模式和作用机制。本项目将为共生菌促进IBD黏膜愈合提供新的理论依据，也为脆弱拟杆菌防治IBD的临床应用奠定基础。

The interaction between enteric commensal microbiota and mucosal epithelium not only influences the progression of inflammatory bowel disease, but also has a key role in mucosal healing. ILC3/IL-22/pSTAT3 axis has been considered as an important signal pathway for mucosal repair mediated by commensal bacteria, but the specific bacteria which make a regulation on it have not been clearly demonstrated. In the previous work, we found that long-time use of antibiotic led to the delay of mucosal healing in experimental colitis, while the bacteroides fragilis we isolated could reverse this process and increased gene expression of IL-22. We speculate that B.fragilis may activate the molecular pathway of ILC3/IL-22 directly or indirectly by regulating the intestinal flora, and then exert its therapeutic function in IBD mucosal healing by promoting the epithelial regeneration. In this project, we plan to construct the mouse model of IBD combined with clinical specimens, transgenic animals and in vitro experiments, to unveil the the regulation pattern and mechanism by which the process of intestinal mucosal healing is affected by the interaction between symbiotic bacteria and bacteria, as well as symbiotic bacteria and Intestinal epithelium. This research will provide a fresh theoretical basis for symbiotic bacteria-mediated IBD mucosal healing, and lay a groundwork for the clinical application of B.fragilis in IBD.