Defining a type II IL-9R

定义 II 型 IL-9R

• 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
• 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

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--定义类型II IL-9R 细胞通过特定的细胞因子受体结合来调节免疫反应和 发炎。以这些相互作用为目标已成为日益增长的患者治疗的有效方法 疾病清单。在细胞因子中，IL-9具有多效性，与变态反应性和自身免疫性疾病有关 在肿瘤免疫方面。在造血细胞中，IL-9通过IL-9Rα链和γc链传递信号 与包括IL-2、IL-4和IL-7在内的其他细胞因子共享。许多报告，包括我们自己的，都证明了 IL-9也能刺激非造血细胞的直接作用。然而，限制造血的人 γc的表达在我们对IL-9如何向非造血细胞传递信号的知识中留下了空白。这个 相关细胞因子IL-4具有由IL-4Rα链和IL-13Rα1链组成的II型受体，以 促进非造血细胞的反应。在本申请中，我们提供了II型IL-9R的证据 建议在非造血细胞中发挥作用。我们推测，在呼吸道上皮细胞上，IL-9Rα可以 与IL-13Rα1结合形成II型受体，我们提供了物理相互作用的初步数据 在这些受体链之间。我们将使用基因靶向的小鼠以及在体外和体内验证这一假说 分析呼吸道上皮细胞中IL-9信号和IL-9功能的活体模型系统。总而言之，这些研究 将扩展细胞因子受体生物学的范例，提供对IL-9效应器功能的详细见解，以及 进一步确定靶向细胞因子受体链如何影响患者群体的免疫力。