Antigen Recognition at Epithelial Interphases

描述（由申请人提供）：这些研究将为粘膜表面中DC的区域特异性调节程序提供新的见解。我们已经鉴定了一种粘膜浆细胞样树突状细胞（pDC）亚群，其在限制肠道炎症从而促进组织重建和粘膜恢复方面具有关键作用。该pDC亚群在结肠炎期间作为肠道中的主要DC亚群出现，以指导炎症消退所必需的粘膜特异性T细胞功能。我们假设粘膜pDC是通过控制Foxp3+ T细胞和Th17细胞的酪氨酸特异性调节表型来调节粘膜修复反应的主要介质。我们将定义关键机制，使调节粘膜pDC有效地抑制炎症信号和介导粘膜保护。定义这个新发现的pDC亚群在调节粘膜炎症中的功能作用将提供对在肠的高抗原性环境中介导组织修复所需的调节性T细胞的粘膜特异性控制的机制的关键见解。 公共卫生相关性： 更精确地定义特化树突状细胞在调节粘膜T细胞中的功能是我们理解控制肠道炎症的机制所必需的。我们将定义一个新发现的粘膜树突状细胞亚群在调节粘膜炎症中的功能作用，为介导组织修复所需的调节性T细胞的粘膜特异性控制机制提供关键的见解。

DESCRIPTION (provided by applicant): These studies will provide new insights into the region specific regulatory programs of DCs in mucosal surfaces. We have identified a mucosal plasmacytoid dendritic cell (pDC) subset that has a critical role in limiting intestinal inflammation thereby promoting tissue reconstruction and mucosal restitution. This pDC subset appears as a major DC subset in the intestine during colitis to direct mucosa-specific T cell functions essential for the resolution of inflammation. We hypothesize that mucosal pDCs are principal mediators of mucosal repair responses by controlling the intestine-specific regulatory phenotypes of Foxp3+ Tregs and Th17 cells. We will define key mechanisms that allow regulatory mucosal pDCs to effectively suppress inflammatory signals and to mediate mucosal protection. Defining the functional role of this newly discovered pDC subset in the regulation of mucosal inflammation will provide pivotal insights into the mechanisms that mediate mucosa specific control of regulatory T cells required for tissue repair in the highly antigenic environment of the intestine. PUBLIC HEALTH RELEVANCE: A more precise definition of the function of specialized dendritic cells in the regulation of mucosal T cells is required for our understanding of the mechanisms which control intestinal inflammation. We will define the functional role of a newly discovered mucosal dendritic cell subset in the regulation of mucosal inflammation to provide pivotal insights into the mechanisms that mediate mucosa-specific control of regulatory T cells required for tissue repair.