干扰素-Apol9通路在结肠炎病理中发挥作用的细胞与分子机制

肠道稳态失衡会导致肠道相关疾病如肠炎的病理。该申请项目拟通过DSS诱导的肠炎模型研究阐明肠道损伤修复在维持肠道稳态平衡中的作用机制。我们的前期工作基础研究发现干扰素-r可以直接诱导载脂蛋白Apol9a和Apol9b（Apol9a/9b，简称Apol9）的表达，干扰素及Apol9的表达都依赖肠道菌群，Apol9促进DSS诱导的肠炎病理并且其作用需要肠道菌群的参与，表明在DSS诱导肠炎病理损伤修复过程中干扰素-Apol9通路与肠道菌群之间存在相互作用。该申请项目将系统阐明它们之间的互作机制，主要包括研究分析DSS诱导肠炎病理过程中干扰素产生的细胞与分子机制，干扰素诱导Apol9表达的细胞与分子机制，Apol9如何影响肠道的损伤修复及肠道菌群平衡进而促进肠炎的病理，以及分析鉴定对应于小鼠Apol9的人源Apol分子。该项目研究成果将为肠炎等相关肠道疾病的治疗提供理论基础、新靶点与策略。

Imbalance of intestinal homeostasis leads to intestinal pathogenesis like inflammatory bowl disease. This grant is proposed to investigate the functional mechanisms of intestinal damage repair in maintaining intestinal homeostasis through utilizing DSS-induced colitis mouse model. We have found that IFN-r could directly induce the expression of apolipoprotein Apol9a and Apol9b (Apol9a/9b, concisely as Apol9), gut microbiota was required for the expression of interferons and Apol9 in the colon, Apol9 promoted DSS-induced colitis pathogenesis through gut microbiota, suggesting that the interferon-Apol9 axis and gut microbiota affect each other during DSS-induced colitis. The grant will systemically investigate the cellular and molecular mechanisms of the interactions of the interferon-Apol9 axis and gut microbiota, including identification of interferons-producing cell types and how interferons are induced by microbiota, the identification of Apol9-producing cell types and how interferons induce Apol9 expression, how Apol9 affects intestinal damage repair and gut microbiota balance to promote colitis pathogenesis, and the identification of human Apol homologue of mouse Apol9. The grant outcomes will provide important new information, targets and strategies for therapy of colitis.