REGULATION OF MUCOSAL IMMUNE RESPONSES BY ANTIGEN PRESENTING CELLS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这个项目的目的是对肠道中的抗原提呈细胞如何调节粘膜耐受和免疫有更深入的基础了解。推动这项研究的中心假设是，肠道固有层巨噬细胞促进调节性T细胞的诱导和粘膜耐受。 大量的研究表明，IBD的发病机制是一个多因素的过程，至少包括三个主要的相互作用因素：遗传易感因素、环境条件和粘膜免疫功能改变。虽然遗传因素和环境非常难以调查和控制，但人们一直关注和研究IBD的粘膜免疫反应，其工作假设是肠道炎症是由于对正常自体菌群的免疫耐受性下降所致。虽然人们对IBD发病机制的了解越来越多，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，甚至开始设想预防IBD。 一个重要的挑战仍然是在加强肠道耐受性和允许对病原微生物的适当粘膜免疫反应之间保持关键平衡的能力。粘膜常驻抗原提呈细胞，特别是树突状细胞(DC)和巨噬细胞，在这方面很有希望，因为它们可以摄取肠道细菌并诱导不同类型的免疫反应。本质上，粘膜APC是位于上皮屏障下方的哨兵，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.