致病菌发生肠外移位是急性胰腺炎继发脓毒血症(SEPSIS)、多脏器功能衰竭(MOF)的重要因素。其机理为肠道机械及免疫屏障功能障碍。研究发现小肠上皮细胞（intestinal epithelial cells, IECs）在构筑了机械屏障的同时亦能通过其Toll样受体-5（Tlr5）激活参与肠道局部免疫及细菌分布的调节。故课题组拟在急性胰腺炎合并肠道细菌移位的小鼠模型平台上，采用条件性基因敲除（Tlr5 f/f）技术、体外共刺激诱导淋巴细胞分化以及生物荧光标记细菌示踪等技术进一步明确IECs及其Tlr5信号系统直接或在肠粘膜下树突状细胞（lamina propria dendritic cells, LPDCs）辅助下间接调控肠道免疫状态及细菌移位的机制。其不但为急性胰腺炎继发细菌移位提供科学解释，更有可能为开发以IECs为靶标的新型免疫治疗提供理论依据。

Intestinal bacterial translocation occurs in severity acute pancreatitis (SAP) patients play an important role in leading to sepsis and MOF, which bend to the mechanism of intestinal machinery and immune barrier function disorder, and the intestinal mucosal immune injury plays a particularly important role. Several studies found that intestinal epithelial cells (IECs) may not only build machinery barrier but also be involved in regulation of local immune and intestinal bacteria distribution through Toll-like receptor 5 (Tlr5) activation. On the basis of a model of SAP combined with intestinal bacterial translocation, we try to clarify the mechanism of intestinal immune barrier function disorder and bacterial translocation been directly or indirectly (with the help of lamina propria dendritic cells, LPDCs) regulated by Tlr5 signal system of IECs with techniques of conditional knockout (Tlr5f/f), co-stimulation to induce lymphocyte differentiation and bacterial tracing with biological fluorescent, etc. This work will not only provide an explanation for how SAP leading to intestinal bacterial translocation, more likely for the future of providing the theoretical basis for a new type of immunotherapy targets at IECs.