Interleukin-2 regulation of mucosal inflammation

IL-2对粘膜炎症的调节

基本信息

批准号：
10161723
负责人：
Gregory F Sonnenberg
金额：
$ 54.34万
依托单位：
WEILL MEDICAL COLL OF CORNELL UNIV
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-06-06 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10161723
关键词：
Acute Address Affect American Antigen Presentation Antigens Biological Chronic Clinic Clinical Crohn&apos s disease of the ileum Data Development Distal part of ileum Food Hypersensitivity Gastrointestinal tract structure Health Care Costs Homeostasis Human Hypersensitivity Immune Tolerance Immune response Immunity Immunologics In Vitro Inflammation Inflammatory Inflammatory Bowel Diseases Interleukin-1 beta Interleukin-2 Intestines Investigation Knowledge Large Intestine Location Lymphoid Lymphoid Cell Lymphoid Tissue Malignant Neoplasms Mammals Microbe Mucositis Mucous Membrane Mus Pathogenesis Pathway interactions Patients Phenotype Production Regulation Regulatory T-Lymphocyte Reporter Research Research Proposals Role Seminal Small Intestines Source T-Cell Activation T-Lymphocyte TSLP gene Therapeutic Tissues base cytokine dietary graft vs host disease human disease in vivo inflammatory disease of the intestine innovation loss of function mutation microbial microbiota mucosal site novel novel strategies oral tolerance prevent response tool

项目摘要

PROJECT ABSTRACT Uncontrolled inflammation at mucosal sites underlies the pathogenesis and progression of multiple chronic human diseases including allergy, hypersensitivity, inflammatory bowel disease (IBD), cancer and graft-versus- host-disease (GVHD), and there is an urgent need to develop novel approaches to prevent, limit or reverse mucosal inflammation. Interleukin-2 (IL-2) is a pleiotropic cytokine that profoundly influences immunologic tolerance in mammals, and modulation of IL-2 is currently being developed as a therapeutic approach in the clinic. Since its discovery, a majority of research has focused on how IL-2 influences T cell activation or supports regulatory T cells (Tregs) within lymphoid tissues. Despite these advances, the critical cellular sources and functional regulation of IL-2 production at mucosal sites remains poorly defined. The fundamental focus of this research proposal is to interrogate novel cellular sources of IL-2 that critically influence immunologic homeostasis and inflammation within the mammalian gastrointestinal (GI) tract. We will employ innovative approaches and develop new tools to define the role and regulation of mucosal IL-2 during homeostasis or following intestinal inflammation and food allergy. Collectively, results from these studies will define the regulation and functional significance of novel cellular sources of IL- 2 within the intestine. These findings will critically inform ongoing therapeutic approaches to augment IL-2, or provoke the development of novel tractable strategies to promote tolerance and control mucosal inflammation.

项目摘要粘膜部位的不受控制的炎症是多个慢性的发病机理和进展人类疾病，包括过敏，超敏反应，炎症性肠病（IBD），癌症和移植物 - 宿主 - 疾病（GVHD），迫切需要开发新颖的方法来预防，限制或逆转粘膜炎症。白介素2（IL-2）是一种多效细胞因子，对免疫学产生深远的影响哺乳动物的耐受性，以及IL-2的调节目前正在作为一种治疗方法开发诊所。自发现以来，大多数研究都集中在IL-2如何影响T细胞激活或支持淋巴组织中调节性T细胞（Tregs）。尽管有这些进展，但关键的细胞粘膜位点IL-2产生的来源和功能调节仍然很差。这该研究建议的基本重点是审问新型的IL-2细胞来源哺乳动物胃肠道内的免疫稳态和炎症严重影响（gi）道。我们将采用创新方法并开发新工具来定义粘膜IL-2在稳态或肠炎和食物过敏之后。总体上，结果从这些研究中，将定义IL-新型细胞来源的调节和功能意义 2在肠内。这些发现将严重告知正在进行的治疗方法以增强 IL-2，或激发新的可拖动策略以促进宽容和控制粘膜炎症。