THE ROLE OF ANTIGEN PRESENTING CELLS IN MODULATING INTESTINAL IMMUNE RESPONSES

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。 在了解IBD的肠道免疫反应方面，一个重要的挑战仍然是清楚地了解在加强肠道耐受，同时允许对病原微生物进行适当的粘膜免疫反应之间的关键免疫平衡。粘膜常驻抗原提呈细胞，特别是树突状细胞和巨噬细胞，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，例如促炎(Th1/Th17)和调节性(Treg/TR1/Th3)T细胞反应。然而，固有层抗原提呈细胞群体及其功能仍未得到充分界定。因此，该项目的总体目标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。 我们继续专注于对特性不佳的固有层巨噬细胞群体的彻底调查，并将它们与粘膜树突状细胞进行比较。推动这项研究的中心假设是，肠道固有层巨噬细胞独特的抗炎信号可能促进调节性T细胞的诱导和粘膜耐受。通过分析固有层巨噬细胞在体外和体内调节T细胞反应的能力(特异性目标1)，评估它们在口腔耐受和肠道炎症中的作用(特异性目标2)，通过比较粘膜巨噬细胞和DC重叠和不同的性质和功能(特异性目标3)，继续检验这一假说。 从这些研究中获得的信息继续代表着对肠道抗原提呈细胞功能的理解的重大进展，因为它们与诱导耐受和免疫原性免疫反应有关。这些知识最终可能有助于合理设计治疗IBD的免疫疗法。

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. An important challenge in understanding intestinal immune responses in IBD remains achieving a clear understanding of the critical immunological balance between enforcing intestinal tolerance, while allowing for appropriate mucosal immune responses to pathogenic microbes. Mucosa resident antigen presenting cells, particularly dendritic cells and macrophages, hold great promise in this regard because they can uptake enteric bacteria and induce distinct types of immune responses, for example pro-inflammatory (Th1/Th17) versus regulatory (Treg/Tr1/Th3) T cells responses. However, lamina propria antigen presenting cell populations and their functions remain inadequately defined. Therefore, the overall objective of this project has been to gain a stronger fundamental understanding of how antigen presenting cells in the intestine function to modulate mucosal tolerance and immunity. We have continued to focus on the thorough investigation of the poorly characterized population of lamina propria macrophages and to compare them to mucosal DCs. The central hypothesis driving this research has been that the unique anti-inflammatory signature of intestinal lamina propria macrophages may promote the induction of regulatory T cells and mucosal tolerance. This hypothesis continues to be tested by analyzing the ability of lamina propria macrophages to modulate T cell responses in vitro and in vivo (Specific Aim 1), assessing their role in oral tolerance and intestinal inflammation (Specific Aim 2) and by comparing of overlapping and distinct qualities and functions of mucosal macrophages and DCs (Specific Aim 3). Information gained from these studies continues to represent major advancements in the understanding of intestinal antigen presenting cell functions as they relate to the induction of tolerogenic and immunogenic immune responses. This knowledge could ultimately aid in the rational design of immunotherapeutics to treat IBD.