克罗恩病（CD）是一类免疫相关肠道炎症疾病，其发病机制尚未阐明，但已发现某些Th细胞亚群参与CD发病，尤其Th17细胞（通过分泌IL-17）是介导CD发生的重要效应细胞。近期文献报道，DLG1-PI3K信号通路可调控Th细胞亚群分化。申报者前期研究也首次发现：CD患者体内DLG1（属膜相关鸟氨酸激酶级联蛋白家族成员）表达水平升高，可能是CD的潜在易感基因。申报者推测：DLG1-PI3K信号途径可能通过诱导IL-17+T细胞（包括Th17细胞、IL-17+Treg）分化而参与CD发病。为此，本项目拟建立野生小鼠CD及敲除DLG1基因的小鼠CD模型，应用PI3K抑制剂，探讨DLG1-PI3K通路对IL-17+T细胞亚群分化及转化的影响，以阐明DLG1参与CD发病的作用及其机制。本项目从新的角度探讨CD发病机制，可望为探索CD治疗的新靶点提供重要实验依据。

Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract with disturbances in immunoregulation.The pathogenesis of CD remains unclear. It is thought that helper T cell subsets participate in CD, and Th17 cell is a kind of effect cell of important functions. Recent research reports that a signaling pathway of DLG1-PI3K may regulate differentiation of Th cell subsets. We have reported DLG1 as a potential susceptibility gene for CD in the Chinese population for the first time, and have detected higher expression of DLG1 (a member of the membrane-associated guanylate kinase protein family) in CD patients compared with normal controls. We speculate that the DLG1-PI3K signaling pathway may take part in pathogenesis of CD via abduction of CD4+IL-17+T cells differentiation (including Th17 cell and IL-17+Tregs). By using the models of DLG1 knockout mice and trinitrobenzene sulphonic acid (TNBS)-induced colitis mice, and applying PI3K inhibitor, this project intends to confirm the impact of DLG1-PI3K signaling pathway on differentiation and transformation of CD4+IL-17+T cells, to clarify the effect and mechanisms of DLG1 gene in immunopathogenesis of CD. The project will provide an important experiment basis for therapy targeting DLG1 from a new perspective to explore the pathogenesis of CD.