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Defining a type II IL-9R

定义 II 型 IL-9R

基本信息

批准号：
10739086
负责人：
MARK H KAPLAN
金额：
$ 23.78万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-05-24 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10739086
关键词：
Acute Allergic Disease Allergic inflammation Autoimmune Diseases Autoimmunity Binding Biochemical Biological Assay Biological Models Biology Cell Communication Cells Chronic Communication Complex Cytokine Receptor Binding Cytokine Receptors Data Development Dimerization Disease Epithelial Cells Erythropoietin Exposure to Family Gene Activation Gene Expression Gene Targeting Hematopoietic IL-13Ralpha1 IL7 gene Immune response Immunity In Vitro Inflammation Inflammatory Interleukin 2 Receptor Interleukin-15 Interleukin-2 Interleukin-4 Interleukin-9 Knowledge Left Lung Mediating Mediator Modeling Mus Mutant Strains Mice Organ Patients Process Proliferating Pulmonary Inflammation Reporting STAT protein Signal Pathway Signal Transduction Smooth Muscle Myocytes Structure Testing Tracheal Epithelium Tumor Immunity airway epithelium cell type cytokine flexibility immune function in vivo in vivo Model insight interleukin-21 intestinal epithelium patient population protein activation receptor response

项目摘要

PROJECT SUMMARY / ABSTRACT – Defining a type II IL-9R Cells communicate through specific cytokine-receptor binding to mediate immune responses and inflammation. Targeting these interactions has become an effective approach to patient treatment in a growing list of diseases. Among the cytokines, IL-9 is pleiotropic and is involved in allergic and autoimmune diseases and in tumor immunity. In hematopoietic cells IL-9 signals through the IL-9Rα chain and the γc chain that is shared with other cytokines including IL-2, IL-4, and IL-7. Numerous reports, including our own, demonstrate the ability of IL-9 to stimulate direct effects in non-hematopoietic cells as well. Yet, the hematopoietic-restricted expression of γc leaves a gap in our knowledge of how IL-9 delivers a signal to non-hematopoietic cells. The related cytokine IL-4 has a type II receptor that is composed of the IL-4Rα chain and the IL-13Rα1 chain to facilitate responses in non-hematopoietic cells. In this application we provide evidence of a type II IL-9R that is proposed to function in non-hematopoietic cells. We hypothesize that on airway epithelial cells IL-9Rα can combine with IL-13Rα1 to form a type II receptor and we provide preliminary data of a physical interaction between these receptor chains. We will test this hypothesis using gene-targeted mice and both in vitro and in vivo model systems to analyze IL-9 signaling and IL-9 function in airway epithelial cells. Together, these studies will expand the paradigm of cytokine receptor biology, provide detailed insight into IL-9 effector functions, and further define how targeting cytokine receptor chains impacts immunity in the patient population.

项目摘要/摘要-界定II型IL-9R