Antigen Recognition at Epithelial Interphases

上皮间期的抗原识别

基本信息

批准号：
8049091
负责人：
HANS-CHRISTIAN REINECKER
金额：
$ 36.36万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-07-01 至 2014-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8049091
关键词：
Antigens Cell physiology Cells Characteristics Colitis Colon Data Dendritic Cells Endoscopy Environment Epithelial Exhibits Fluorescence Gene Expression Gene Expression Profiling Goals Granulocyte Colony-Stimulating Factor Immune Immune system Immunosuppression In Vitro Inflammation Inflammatory Inflammatory disease of the intestine Interferons Interleukin-10 Interleukin-17 Interleukin-6 Interphase Intestines Knockout Mice Lamina Propria Ligands Link Maintenance Mediating Mediator of activation protein Microscopic Mucositis Mucous Membrane Mus Outcome Parabiosis Pathway interactions Phenotype Production Regulation Regulatory T-Lymphocyte Reporter Resolution Role Signal Transduction Source Surface T-Cell Activation T-Lymphocyte Testing Wound Healing cytokine in vivo insight interleukin-22 mRNA Expression microbial novel programs public health relevance repaired research study response tissue reconstruction

项目摘要

DESCRIPTION (provided by applicant): These studies will provide new insights into the region specific regulatory programs of DCs in mucosal surfaces. We have identified a mucosal plasmacytoid dendritic cell (pDC) subset that has a critical role in limiting intestinal inflammation thereby promoting tissue reconstruction and mucosal restitution. This pDC subset appears as a major DC subset in the intestine during colitis to direct mucosa-specific T cell functions essential for the resolution of inflammation. We hypothesize that mucosal pDCs are principal mediators of mucosal repair responses by controlling the intestine-specific regulatory phenotypes of Foxp3+ Tregs and Th17 cells. We will define key mechanisms that allow regulatory mucosal pDCs to effectively suppress inflammatory signals and to mediate mucosal protection. Defining the functional role of this newly discovered pDC subset in the regulation of mucosal inflammation will provide pivotal insights into the mechanisms that mediate mucosa specific control of regulatory T cells required for tissue repair in the highly antigenic environment of the intestine. PUBLIC HEALTH RELEVANCE: A more precise definition of the function of specialized dendritic cells in the regulation of mucosal T cells is required for our understanding of the mechanisms which control intestinal inflammation. We will define the functional role of a newly discovered mucosal dendritic cell subset in the regulation of mucosal inflammation to provide pivotal insights into the mechanisms that mediate mucosa-specific control of regulatory T cells required for tissue repair.

描述（由申请人提供）：这些研究将为粘膜表面中DC的特定区域调节计划提供新的见解。我们已经确定了一个粘膜浆细胞性树突状细胞（PDC）子集，该子集在限制肠道炎症中具有关键作用，从而促进组织的重建和粘膜恢复。该PDC子集是结肠炎期间肠道中的主要DC子集，用于指导粘膜特异性T细胞功能对于炎症的溶液至关重要。我们假设粘膜PDC是通过控制Foxp3+ Treg和Th17细胞的肠道特异性调节表型，是粘膜修复反应的主要介体。我们将定义关键机制，以使调节性粘膜PDC有效抑制炎症信号并介导粘膜保护。定义该新发现的PDC子集在粘膜炎症调节中的功能作用将提供关键见解，以介导粘膜在高度抗原性环境中介导粘膜特异性控制细胞所需的调节性T细胞。公共卫生相关性：我们了解控制肠道炎症的机制需要更精确的树突状细胞在调节粘膜T细胞调节中的功能的更精确的定义。我们将定义新发现的粘膜树突状细胞子群在粘膜炎症调节中的功能作用，以提供介导粘膜特异性控制组织修复所需的调节性T细胞的机制的关键见解。