REGULATION OF MUCOSAL IMMUNE RESPONSES BY ANTIGEN PRESENTING CELLS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 这个项目的目的是获得一个更强的基本了解如何在肠道抗原呈递细胞的功能，以调节粘膜耐受性和免疫力。推动这项研究的中心假设是肠固有层巨噬细胞促进调节性T细胞和粘膜耐受的诱导。 大量的观察已经确定IBD的发病机制是一个多因素的过程，包括至少三个主要的相互作用的因素：遗传易感性因素，环境条件和改变粘膜免疫功能。虽然遗传因素和环境非常难以调查和控制，但重要的注意力和研究调查集中在理解IBD中的粘膜免疫应答上，工作假设是肠道炎症是由于对正常自体植物群的免疫耐受性的破坏。虽然对导致IBD发病机制的因素的了解越来越多，但迫切需要更彻底地了解控制炎症的保护性因素，以便设计更有效的治疗方法，甚至开始设想IBD的预防。 一个重要的挑战仍然是保持在加强肠道耐受性之间的关键平衡的能力，同时允许对病原微生物的适当粘膜免疫应答。粘液驻留抗原呈递细胞， 特别是树突状细胞（DC）和巨噬细胞在这方面具有很大的前景，因为它们可以摄取肠道细菌并诱导不同类型的免疫应答。本质上，粘膜APC是位于细胞膜下方的哨兵。 上皮屏障，并能够启动和协调肠道免疫反应。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The purpose of this project is to gain a stronger fundamental understanding of how antigen presenting cells in the intestine function to modulate mucosal tolerance and immunity. The central hypothesis that drives this research is that intestinal lamina propria macrophages promote the induction of regulatory T cells and mucosal tolerance. Numerous observations have established that the pathogenesis of IBD is a multifactorial process encompassing at least three major interacting elements: genetic susceptibility factors, environmental conditions, and altered mucosal immune function. While genetic factors and the environment are incredibly difficult to investigate and control, significant attention and research investigation has been focused on understanding mucosal immune responses in IBD with the working hypothesis being that intestinal inflammation results from a breakdown in immune tolerance to normal autologous flora. While there is increasing understanding of the factors that contribute to the pathogenesis of IBD, there is an urgent need for more thoroughly understanding protective factors that control inflammation in order to design more efficacious treatments and to even begin to envision prevention of IBD. An important challenge remains the ability to maintain critical balance between enforcing intestinal tolerance, while allowing for appropriate mucosal immune responses to pathogenic microbes. Mucosal resident antigen presenting cells, particularly dendritic cells (DCs) and macrophages, hold great promise in this regard because they can uptake enteric bacteria and induce distinct types of immune responses. In essence, mucosal APCs are sentinels situated just beneath the epithelial barrier and are capable of initiating and orchestrating intestinal immune responses.