FXYD3介导的信号网络对肠道黏膜免疫稳态的调控研究

高度完整和调节完善的肠道黏膜屏障和免疫系统，在疾病防御中至关重要，但目前肠道黏膜免疫稳态的维持和精细调控机制远未阐明。钠钾泵调节蛋白FXYD3在炎症调控中的作用尚未报道。前期我们发现FXYD3在小鼠肠上皮中特异性缺失可导致炎症性肠病模型显著加重，FXYD3主要表达于杯状细胞，对黏蛋白mucin-2的分泌起到关键调控作用，可能通过活化STAT3信号通路在黏膜屏障和免疫平衡中发挥重要功能。本项目拟利用肠道上皮、免疫细胞条件性敲除FXYD3小鼠的肠道炎症疾病模型，深入研究以FXYD3为核心所介导的信号网络对维持肠道黏膜免疫稳态的关键作用。结合临床样本，分析FXYD3在肠道炎性微环境不同细胞类型中的表达和调控模式，揭示其与肠道炎症疾病进展和治疗的关系。结果有望为进一步阐释肠道黏膜免疫应答的特点和规律，揭示肠道炎症性自身免疫性疾病的发生发展机制提供新的观点和视角，并为疾病治疗提供潜在候选靶点。

High integrity and well-regulated intestinal mucosal barrier and immune system are very important in disease defense, but the maintenance and fine tuning of intestinal mucosal immune homeostasis is far from clarified. The role of Na,K-ATPase regulatory protein FXYD3 in inflammation regulation has not been reported. In previous study, we found that the specific deletion of FXYD3 in the intestinal epithelium of mice can lead to the aggravation of inflammatory bowel disease model. FXYD3 is mainly expressed in goblet cells and plays a key role in the regulation of mucin-2 secretion. It might be an important player in maintenance of mucosal barrier and immune balance by activating STAT3 signaling pathway. This project intends to study the key role of signal networks mediated by FXYD3 in regulating intestinal mucosal immune homeostasis by using intestinal epithelial and various types of immune cell conditional knockout FXYD3 mice with model of intestinal inflammatory disease. Combined with clinical tissue samples, the expression and regulation patterns of FXYD3 in different cell types of intestinal inflammatory microenvironment will be investigated, and the relationship between FXYD3 and the progression and treatment of intestinal inflammatory diseases will be revealed. The results are expected to provide new perspectives and insights for further elucidating the characteristics and patterns of intestinal mucosal immune response, revealing the mechanism of the occurrence and development of intestinal inflammatory autoimmune diseases, and providing potential candidates for disease treatment.