Antigen Recognition at Epithelial Interphases

描述（由申请人提供）：这些研究将为粘膜表面dc的区域特异性调控程序提供新的见解。我们已经确定了一个粘膜浆细胞样树突状细胞（pDC）亚群，它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。在结肠炎期间，这个pDC亚群作为主要的DC亚群出现在肠道中，指导对炎症解决至关重要的粘膜特异性T细胞功能。我们假设粘膜pDCs通过控制Foxp3+ Tregs和Th17细胞的肠道特异性调节表型是粘膜修复反应的主要介质。我们将定义允许调节性粘膜pDCs有效抑制炎症信号和介导粘膜保护的关键机制。确定这一新发现的pDC亚群在粘膜炎症调节中的功能作用，将为在肠道高抗原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提供关键见解。

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.