糖基转移酶EXTL1调控树突状细胞迁移和天然免疫应答的功能和机制研究

天然免疫及炎症调控是目前生命科学界的前沿研究热点。研究树突状细胞（DC）的天然免疫功能的内在平衡调节机制对于深入了解DC免疫功能、寻找DC紊乱介导的炎症性疾病的发病基础具有重要意义。病原体感染后，DC需有效控制炎性因子分泌以避免过度炎症反应，同时，快速迁移至次级淋巴结以启动适应性免疫应答，从而清除病原体。目前，尚不清楚机体通过何种机制对DC成熟活化和趋化功能的平衡进行精密调控，从而及时清除病原体，同时避免不必要的炎症损伤。蛋白质糖基化在免疫应答及疾病调控中发挥重要作用，而其在天然免疫和炎症中的作用及机制尚不清楚。我们前期研究发现，糖基转移酶EXTL1可能在DC成熟及迁移调控中发挥重要作用。基于此，本项目将围绕EXTL1在DC成熟活化和迁移功能中的作用和机制展开研究，以揭示DC介导的炎症反应的新型机制以及蛋白质糖基化在天然免疫中的新型调控功能，为DC相关炎症性疾病提供新的机制解释。

Research of the regulation mechanism of the innate immune function of dendritic cells (DC) is critical for further understanding of DC immune function and the pathogenesis of DC-related inflammatory diseases. During pathogenic infection, DC need to effectively control the secretion of inflammatory cytokines in order to avoid excessive inflammatory response, and at the same time, also needs to rapidly migrate to the secondary lymph nodes to initiate adaptive immune response to eliminate invading pathogens. However, it remains unclear how the immune system precisely regulate the balance between DC maturation/activation and chemotaxis migration in order to eliminate pathogens in time while avoiding unnecessary inflammatory damage. Protein glycosylation plays an important role in immune response and disease regulation, but its role and mechanism in innate immune responses and inflammation are still unclear. In our previous studies, we found that glycosyltransferase EXTL1 may play an important role in the regulation of DC maturation and migration. Therefore, this project will focus on the role and mechanism of EXTL1 in the maturation/activation and migration of DC, in order to reveal the new molecular mechanism of DC-mediated inflammatory response and the new regulatory function of protein glycosylation in innate immune responses, providing new mechanistic explanation and treatment strategies for DC related inflammatory diseases and autoimmune diseases.