Migration and function of Th17 cells in the gut

项目概述：Th 17细胞在免疫、组织炎症和自身免疫中发挥重要作用 疾病肠道是体内Th 17细胞最丰富的器官。因此，调查 Th 17细胞在肠道中的迁移和功能将产生关于Th 17细胞介导的 调节组织炎症和免疫。目前尚不清楚Th 17细胞是如何被诱导、维持 并定位在肠道中。这是我们理解和控制（或利用） 这个重要的T细胞谱系。这项应用的中心假设是， 在调节肠道中Th 17细胞的迁移、诱导和维持中起重要作用。我们 其理由是，将有可能更有效地控制炎症性疾病和感染， 通过调节肠道Th 17细胞的迁移、诱导和维持， 研究已经完成。在转运受体中，我们将重点研究受体CCR 6， 由大多数Th 17细胞特征性表达并特异性结合趋化因子CCL 20 由肠中的滤泡相关上皮细胞和其他特化上皮细胞表达。 有三个目标：具体目标#1。确定CCR 6在肠道中Th 17迁移中的作用; 具体目标#2确定CCR 6在Th 17细胞的诱导、维持和增殖中的作用， #36825;的目标#3。确定Th 17细胞调节CCR 6表达的机制。 预计它将产生关于贩运受体对移徙的要求的新知识， 肠Th 17细胞的诱导和维持。该项目还将提供新的战略，以控制 Th 17细胞的迁移及其在肠道特定解剖部位的分化和活性。这 这个问题对于与肠道相关的炎症病理和感染具有首要重要性 (e.g.炎症性肠病和细菌感染），但对于炎症性肠病和细菌感染也很重要。 其他组织部位的疾病。

Project Summary: Th17 cells play important roles in immunity, tissue inflammation and autoimmune diseases. The intestine is the most Th17 cell-enriched organ in the body. Therefore, investigation into the migration and function of Th17 cells in the gut would yield important information on Th17 cell-mediated regulation of tissue inflammation and immunity. It is unknown how Th17 cells are induced, maintained and localized in the gut. This is a significant problem in our understanding and control (or utilization) of this important T cell lineage. The central hypothesis of this application is that trafficking receptors play important roles in regulation of migration, induction, and maintenance of Th17 cells in the intestine. Our rationale is that it will become possible to more effectively control inflammatory diseases and infection in the gut by regulating the migration, induction and maintenance of gut Th17 cells after the proposed research is completed. Among the trafficking receptors, we will focus our research on CCR6, a receptor that is characteristically expressed by most Th17 cells and binds the chemokine CCL20 specifically expressed by follicle-associated epithelial cells and other specialized epithelial cells in the intestine. There are three aims: Specific aim #1. Determine the role of CCR6 in Th17 migration in the gut; Specific aim #2. Determine the role of CCR6 in induction, maintenance and propagation of Th17 cells in the gut; Specific aim #3. Determine the mechanism by which Th17 cells regulate the expression of CCR6. It is expected to yield novel knowledge regarding the trafficking receptor requirement for migration, induction and maintenance of gut Th17 cells. The project will also provide novel strategies to control the migration of Th17 cells and their differentiation and activities in specific anatomic sites of the gut. This problem has primary importance to the inflammatory pathologies and infection associated with the gut (e.g. inflammatory bowel diseases and bacterial infections) but is important also for inflammatory diseases in other tissue sites as well.