Antigen Recognition at Epithelial Interphases

描述（由申请人提供）：本续期申请旨在支持我们的研究继续进行，旨在阐明肠道中抗菌宿主防御所需的树突状细胞亚群的调控程序。我们最近发现了一种细胞回路，其中粘膜dc与小肠的开孔毛细血管系统相互作用，用于从血液循环通过固有层进入肠淋巴系统的抗原的采样和粘膜炎症的控制。在SI中整合腔内和循环抗原监测表明，粘膜树突状细胞和巨噬细胞可以接收来自肠外的微生物信号，肠道病原体识别可以影响外周免疫反应。本提案的重点将是粘膜Zbtb46+ DC中的外源核酸识别途径，包括不同的经典DC亚群，这些亚群可以诱导粘膜免疫系统中表达IL-17的T辅助细胞（Th17）细胞，但也可以驱动诱导的T调节细胞发育和IL-10表达。确定这些关键机制对于制定控制肠道炎症的策略非常重要，同时也有助于理解

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.