白介素-17在自身免疫病病理中发挥作用的细胞与分子机制

IL-17在自身免疫病病理中显著升高而阻断IL-17的功能能降低自身免疫病病理。然而，目前还不清楚在各种自身免疫病病理中IL-17发挥作用的关键靶细胞类群及其分子作用机制。该项目将通过以下研究手段来回答这一关键科学问题，包括：1）通过建立IL-17受体（IL-17RA和IL-17RC）细胞特异性的基因敲除小鼠和自身免疫病模型，研究阐明自身免疫病病理中IL-17发挥作用的关键细胞类型；2）通过小鼠体内和细胞体外模型研究自身免疫病病理微环境中IL-17与其他因子（如bFGF、TNF等）之间的协作与机制；3）筛选与鉴定IL-17信号通路中新的信号分子；4）通过临床自身免疫病病人样本分析验证上述研究中发现的IL-17发挥作用的靶细胞与分子机制。这些研究将系统阐明IL-17在自身免疫病病理中发挥作用的细胞与分子机制，为自身免疫病的治疗提供重要的理论基础，新靶标和新策略。

IL-17 is dramatically increased in multiple autoimmune diseases and blockage of IL-17-mediated function severely reduces autoimmune pathogenesis. However, it is not clear what are the key IL-17 target cell populations and how IL-17 functions during autoimmune pathogenesis. This grant proposes to address the key issue with the following studies, including: 1) finding out the key target cell types of IL-17 through generating the cell type specific gene knockout of IL-17 receptors (IL-17RA and IL-17RC respectively) and analyzing the pathogenesis of those mice after autoimmune disease induction. 2) Investigating the co-operational mechanisms of IL-17 with other factors (such as bFGF and TNF) in the autoimmune microenvironment through in vivo mouse model and in vitro cell culture model. 3) Screening and identifying new signaling molecules in IL-17- mediated signal transduction. 4) Analyzing clinic autoimmune samples to confirm the results from mouse in vivo and cell culture in vitro models. These intestigations will demonstrate the cellular and molecular mechanisms of IL-17- mediated functions in autoimmune pathogenesis, providing important information for new therapeutic strategies.