艰难梭菌是院内感染和抗生素相关腹泻最重要的病原菌。肠上皮细胞在抵抗艰难梭菌感染中发挥关键作用，但分子免疫机制不详。最近发现IL-27是一种重要的免疫调节因子。预实验显示IL-27特异性受体缺陷小鼠在艰难梭菌感染时，死亡率显著上升，且肠上皮细胞内cathelicidin分子CRAMP的表达显著下调。由此提出“IL-27诱导肠上皮细胞表达cathelicidin分子LL-37/CRAMP，介导肠道免疫，抵抗艰难梭菌感染”的科学假说。本项目拟用大宗临床样本明确IL-27表达在艰难梭菌感染发病中的临床意义；并以基因敲除小鼠和原代肠上皮细胞等为研究模型，通过流式细胞分析、抗体阻断、表达谱芯片、siRNA和EMSA等技术，在分子、细胞和动物水平上揭示“IL-27诱导肠上皮细胞表达LL-37/CRAMP而抵抗艰难梭菌感染”的作用及分子信号机制，以期为艰难梭菌感染的诊治研究找到重要线索。

Clostridium difficile is a leading cause of nosocomial infection and antibiotic-associated diarrhea. The immunity mediated by intestinal epithelial cells plays an important role in combating Clostridium difficile infection. However, its molecular and immunoregulatory mechanisms remain to be elucidated. IL-27 is a recently described immunoregulatory cytokine. Our preliminary studies have demonstrated that the mortality rate of IL-27R-deficient mice was significantly higher than that of wild-type mice upon Clostridium difficile infection. Furthermore, the expression of antimicrobial peptide cathelicidin LL-37/CRAMP was significantly down-regulated in IL-27R-deficient intestinal epithelial cells. Therefore, we hypothesize that IL-27 stimulates the expression of cathelicidin LL-37/CRAMP in intestinal epithelial cells, which mediates intestinal immunity against Clostridium difficile infection. In this study, we will evaluate the clinical significance of IL-27 expression in a large cohort of patients with Clostridium difficile infection. Furthermore, we will use various gene knockout mice and primary intestinal epithelial cells to investigate the role of IL-27 in regulating cathelicidin LL-37/CRAMP expression from intestinal epithelial cells in combating Clostridium difficile infection and its potential intracellular signaling pathways by use of flow cytometry analysis, antibody-blocking technology, cDNA microarray,siRNA and EMSA, etc. Our work will provide new strategies for the diagnosis and treatment of Clostridium difficile infection.