Antigen Recognition at Epithelial Interphases

描述(由申请人提供)：此续签申请寻求支持我们的研究的继续，旨在阐明肠道抗菌宿主防御所需的树突状细胞亚群的调节程序。我们最近发现了一种细胞回路，粘膜树突状细胞与小肠有窗的毛细血管系统相互作用，以采集从血液循环通过固有层进入肠道淋巴系统的抗原，并控制粘膜炎症。肠腔抗原和循环抗原监测在SI中的整合表明，粘膜树突状细胞和巨噬细胞可以接收来自肠道外的微生物信号，肠道病原体识别可能会影响外周免疫反应。这一建议的重点将是粘膜Zbtb46+DC中的外来核酸识别途径，包括独特的经典DC亚群，这些DC亚群可以诱导黏膜免疫系统中表达IL-17的T辅助细胞(Th17)，但也可以驱动可诱导的T调节细胞的发育和IL-10的表达。确定这些关键机制对于控制肠道炎症的策略是重要的，而且对于理解 黏膜免疫反应对炎症性肠病外周免疫系统和肠外表现的影响。

DESCRIPTION (provided by applicant): This renewal application seeks support for the continuation of our studies designed to elucidate the regulatory programs of dendritic cell subsets that are required for antimicrobial host defenses in the intestine. We recently discovered a cellular circuitry, whereby mucosal DCs interact with the fenestrated capillary vessel system of the small intestine for the sampling of antigens that transition from the blood circulation through the lamina propria into the intestinal lymphatic system and the control of mucosal inflammation. The integration of luminal and circulatory antigen surveillance in the SI indicates that mucosal dendritic cells and macrophages could receive microbial signals that originate outside the intestine and that intestinal pathogen recognition could impact peripheral immune responses. The focus of this proposal will be the foreign nucleic acid recognition pathways in mucosal Zbtb46+ DCs that include distinct classical DC subsets that can induce IL-17 expressing T helper cells (Th17) cells in the mucosal immune system but also drive inducible T regulatory cell development and IL-10 expression. Defining these pivotal mechanisms is important for strategies that can control intestinal inflammation but also for the understanding of the impact of mucosal immune responses on the peripheral immune system and extra intestinal manifestation of inflammatory bowel diseases.