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Migration and function of Th17 cells in the gut

Th17 细胞在肠道中的迁移和功能

基本信息

批准号：
7930000
负责人：
CHANG H KIM
金额：
$ 33.57万
依托单位：
PURDUE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-15 至 2010-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7930000
关键词：
Anatomic Sites Antigen-Presenting Cells Area Attention Autoimmune Diseases Bacterial Infections Binding Biology CCL20 gene CCR6 gene Cecum Cell Communication Cell Count Cell Lineage Cells Data Disease Distal Epithelial Epithelial Cells Generations Genus Cola Goals Gut associated lymphoid tissue Homing Human Immigration Immune Immune response Immune system Immunity Immunotherapy Infection Inflammation Inflammatory Inflammatory Bowel Diseases Interleukin-17 Intestines Investigation Knowledge Lamina Propria Ligands Lymphoid Follicle Lymphoid Tissue Maintenance Mediating Mucous Membrane Mus Muscle Organ Outcome Pathogenesis Pathology Patients Phenotype Play Process Production Property Publications Regulation Reporting Research Role Site Specialized Epithelial Cell Specificity Stem cells Structure of aggregated lymphoid follicle of small intestine T-Lymphocyte Therapeutic Effect Tissues Tretinoin antimicrobial cancer cell cell motility cell type chemokine chemokine receptor cytokine experience ileum innovation interleukin-23 jejunum migration novel novel strategies pathogen prevent receptor tissue tropism trafficking

项目摘要

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.

项目概要：Th17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 Th17 细胞最丰富的器官。因此，调查 Th17 细胞在肠道中的迁移和功能将产生有关 Th17 细胞介导的重要信息组织炎症和免疫的调节。尚不清楚 Th17 细胞是如何诱导、维持的并定位于肠道。这是我们理解和控制（或利用）这个重要的T细胞谱系。该应用的中心假设是转运受体发挥作用在肠道中 Th17 细胞的迁移、诱导和维持的调节中发挥重要作用。我们的理由是，将有可能更有效地控制炎症性疾病和感染通过调节肠道 Th17 细胞的迁移、诱导和维持来调节肠道研究已完成。在贩运受体中，我们将重点研究CCR6，这是一种受体大多数 Th17 细胞特有表达并特异性结合趋化因子 CCL20 由肠道中的滤泡相关上皮细胞和其他特殊上皮细胞表达。共有三个目标：具体目标#1。确定CCR6在Th17肠道迁移中的作用；具体目标#2。确定 CCR6 在 Th17 细胞诱导、维持和增殖中的作用肠道；具体目标#3。确定 Th17 细胞调节 CCR6 表达的机制。预计将产生关于迁移的运输受体需求的新知识，肠道 Th17 细胞的诱导和维持。该项目还将提供新的策略来控制 Th17 细胞的迁移及其在肠道特定解剖部位的分化和活动。这该问题对与肠道相关的炎症病理和感染具有首要意义（例如炎症性肠病和细菌感染），但对于炎症性肠病也很重要其他组织部位的疾病也是如此。