IL-22通过YAP促进受损肠上皮细胞修复的机制研究

肠黏膜屏障功能与炎症性肠病的发病密切相关，研究表明炎症因子IL-22能够修复肠黏膜屏障，缓解炎症性肠病。然而IL-22调节肠上皮细胞增殖分化、促进受损上皮修复的机制尚不完全清楚。我们前期研究发现IL-22主要通过促进EdU+瞬时扩增（TA）细胞，而非Lgr5+成体干细胞快速增殖。预实验进一步发现IL-22促进了胚胎样干细胞（fetal-like stem cells）的大量生成，是TA细胞的主要组分，且这一过程与YAP/TAZ通路的激活相关。最新研究表明，胚胎样干细胞在肠上皮损伤后修复过程中发挥了重要作用。由此我们提出假设：IL-22通过激活YAP/TAZ通路促进胚胎样干细胞的产生，从而修复受损肠上皮细胞。本项目将采用肠类器官、基因修饰小鼠模型及临床样本等，系统研究IL-22如何促进受损肠上皮细胞增殖和修复的机制，并以此为靶点探索治疗炎症性肠病的新策略。

The function of the intestinal mucosal barrier is closely related to the onset of inflammatory bowel disease. Studies have shown that the inflammatory cytokine IL-22 is helpful to repair the intestinal mucosal barrier and relieve inflammatory bowel disease. However, the mechanism by which IL-22 regulates the proliferation and differentiation of intestinal epithelial cells and promotes the repair of damaged epithelial cells is not fully understood. Our previous studies found that IL-22 mainly promotes the rapid proliferation of EdU+ transient amplifying (TA) cells, rather than Lgr5+ adult stem cells. Preliminary experiments further found that IL-22 promotes the production of fetal-like stem cells, which are the main component of TA cells, which is closely related to the activation of the YAP/TAZ pathway. Recent studies have shown that fetal-like stem cells play an important role in the repair of intestinal epithelium after injury. Therefore, we hypothesized that IL-22 can promote the production of fetal-like stem cells by activating the YAP/TAZ pathway, thus repairing damaged intestinal epithelial cells. This project will use intestinal organoids, genetically modified mouse models and clinical samples to systematically study the mechanism how IL-22 promotes the proliferation and repair of damaged intestinal epithelial cells. Our long-term goal is to use IL-22 as a target to explore the new strategy for the treatment of inflammatory bowel disease.