白介素-17在肠道粘膜免疫中的功能机制

IL-17在肠炎和肠道感染中发挥重要的保护作用。然而，IL-17在肠道粘膜免疫中发挥作用的细胞与分子机制还不清楚。我们的前期工作发现，IL-17与肠炎及肠道感染微环境中上调的细胞因子IL-22、生长因子FGF2之间存在协作，并且它们在肠炎或者肠道感染小鼠模型中也发挥着类似的保护作用。该申请将通过全身基因敲除小鼠及细胞特异性基因敲除小鼠建立肠炎或者肠道感染模型，整合小鼠体内研究体系、细胞体外研究体系等手段研究：1）IL-17在肠炎或者肠道感染中发挥保护作用的关键靶细胞类群及作用机制；2）肠炎或者肠道感染微环境中IL-17与其他因子之间的协作与机制。这些研究将系统阐明IL-17在肠道粘膜免疫及肠道稳态维持中发挥保护作用的细胞与分子机制，为相关肠道疾病的防治提供重要的理论基础，新的治疗靶标和策略。

IL-17 plays an important role in protection against colitis and intestinal infection. However, it is still not clear how IL-17 functions in the protective gut mucosal immunity. Our previous work and preliminary data show that IL-17 as well as IL-22 and FGF2 were up-regulated and they play similar protective roles during DSS-induced colitis or Citrobacter intestinal infection. This grant will utilize complete or cell-type specific gene knockout mice to set up DSS-induced colitis or Citrobacter infection models and integrate the approaches of mouse in vivo models and cell culture in vitro system to identify key target cell types by IL-17 and investigate the molecular mechanisms of the co-operation of IL-17 with other factors in the microenvironment during the colitis or intestinal infection. These studies will demonstrate the cellular and molecular mechanisms of IL-17 in protective intestinal mucosal immunity and maintenance of gut homeostasis to provide important new information for preventive and therapeutic strategies.