Interleukin-2 regulation of mucosal inflammation

IL-2对粘膜炎症的调节

基本信息

批准号：
10409681
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/10409681
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 gut inflammation human disease in vivo 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.

项目摘要粘膜部位不受控制的炎症是多种慢性疾病的发病机制和进展的基础人类疾病，包括过敏、超敏反应、炎症性肠病 (IBD)、癌症和移植物抗- 宿主疾病（GVHD），迫切需要开发新的方法来预防、限制或逆转粘膜炎症。白细胞介素-2 (IL-2) 是一种多效性细胞因子，对免疫学产生深远影响哺乳动物的耐受性，目前正在开发 IL-2 的调节作为治疗方法诊所。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内的调节性 T 细胞 (Treg)。尽管取得了这些进步，关键的细胞粘膜部位 IL-2 产生的来源和功能调节仍不清楚。这该研究计划的基本重点是探究 IL-2 的新细胞来源，严重影响哺乳动物胃肠道内的免疫稳态和炎症（胃肠）道。我们将采用创新方法并开发新工具来定义体内平衡期间或肠道炎症和食物过敏后的粘膜 IL-2。综合来看，结果这些研究将确定IL-的新型细胞来源的调节和功能意义 2.肠道内。这些发现将为正在进行的治疗方法提供重要信息，以增强 IL-2，或激发新的易处理策略的开发以促进耐受和控制粘膜炎症。