胰腺腺泡细胞－树突状细胞转分化及mTOR-TU.1调控与重症急性胰腺炎早期损伤关系

近年来多项临床研究发现：对于重症急性胰腺炎病人，若能早期阻断其病程进展能显著降低死亡率并改善预后，但是目前临床上缺乏针对早期阶段的有效治疗靶点。本课题组前期研究工作发现，在重症急性胰腺炎早期阶段，胰腺腺泡上皮细胞显著表达DC-SIGN并存在“上皮－树突状细胞转分化”现象。同时在大肠、小肠、胃等消化道器官的早期炎症反应中，若用雷帕霉素阻断DC-SIGN，病理严重程度显著下降。因此我们推测在重症急性胰腺炎病程中，DC-SIGN作为“上皮-树突状细胞转分化”现象的标志性分子，在炎症起始阶段起到重要的免疫激活作用。本课题组拟研究“上皮-树突状细胞转分化”和重症急性胰腺炎早期损伤的关系以及DC-SIGN对初始CD4 T细胞的激活作用及其机制，同时探讨mTOR-PU.1途径对“上皮-树突状细胞转分化”现象的介导作用。DC-SIGN及其上、下游通路的研究，将为临床阻断重症急性胰腺炎始动阶段提供新的靶点。

Clinical studies have found, the early blocking progression can significantly reduce the mortality and improve the prognosis of severe acute pancreatitis patient, but there are lack of effective therapeutic targets of the early stages of SAP. Our previous work has found that in the early stage of SAP, pancreatic acinar epithelium cells significant express DC-SIGN and present epithelium-dendritic cell transdifferentiation phenomenon. Meanwhile in the early phase of inflammatory reaction of intestine, stomach and other digestive organs, if DC-SIGN was blocked by Rapamycin, pathological severity significantly decreased. Therefore, we speculate that in the early stage of SAP, as the iconic molecule of epithelium-dendritic cell transdifferentiation phenomenon, DC-SIGN plays an important role in immune regulation at the initial stage of inflammation. Our group intends to investigate the connection between epithelium-dendritic cell transdifferentiation and the early stage of SAP, and to research the mechanism of DC-SIGN activating naïve CD4+ T cell and the mediated role of mTOR-PU.1 pathway of epithelium-dendritic cell transdifferentiation. The research of DC-SIGN and its upstream and downstream pathways, is to provide a new clinical target of blocking initiate stage of SAP, thereby blocking the pathological process and improving the prognosis.