Defining a type II IL-9R
定义 II 型 IL-9R
基本信息
- 批准号:10739086
- 负责人:
- 金额:$ 23.78万
- 依托单位:
- 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:
- 关键词:AcuteAllergic DiseaseAllergic inflammationAutoimmune DiseasesAutoimmunityBindingBiochemicalBiological AssayBiological ModelsBiologyCell CommunicationCellsChronicCommunicationComplexCytokine Receptor BindingCytokine ReceptorsDataDevelopmentDimerizationDiseaseEpithelial CellsErythropoietinExposure toFamilyGene ActivationGene ExpressionGene TargetingHematopoieticIL-13Ralpha1IL7 geneImmune responseImmunityIn VitroInflammationInflammatoryInterleukin 2 ReceptorInterleukin-15Interleukin-2Interleukin-4Interleukin-9KnowledgeLeftLungMediatingMediatorModelingMusMutant Strains MiceOrganPatientsProcessProliferatingPulmonary InflammationReportingSTAT proteinSignal PathwaySignal TransductionSmooth Muscle MyocytesStructureTestingTracheal EpitheliumTumor Immunityairway epitheliumcell typecytokineflexibilityimmune functionin vivoin vivo Modelinsightinterleukin-21intestinal epitheliumpatient populationprotein activationreceptorresponse
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.
项目概要/摘要-定义II型IL-9 R
细胞通过特异性精氨酸受体结合来介导免疫应答,
炎症针对这些相互作用已成为一种有效的方法,以病人的治疗,在日益增长的
疾病清单。在细胞因子中,IL-9是多效性的,并且参与变应性和自身免疫性疾病
和肿瘤免疫。在造血细胞中,IL-9通过IL-9 R α链和γc链发出信号,
与其他细胞因子包括IL-2、IL-4和IL-7共享。包括我们自己在内的许多报告表明,
IL-9在非造血细胞中刺激直接作用的能力。然而,
γc的表达在我们关于IL-9如何向非造血细胞传递信号的知识中留下了空白。的
相关细胞因子IL-4具有由IL-4 R α链和IL-13 R α1链组成的II型受体,
促进非造血细胞的反应。在本申请中,我们提供了II型IL-9 R的证据,
在非造血细胞中发挥作用。我们假设在气道上皮细胞上,IL-9 R α可以
联合收割机与IL-13 R α1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小鼠在体外和体内测试这一假设。
体内模型系统来分析气道上皮细胞中的IL-9信号传导和IL-9功能。这些研究一起
将扩展细胞因子受体生物学的范式,提供IL-9效应器功能的详细见解,
进一步定义靶向细胞因子受体链如何影响患者群体的免疫力。
项目成果
期刊论文数量(0)
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会议论文数量(0)
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{{ truncateString('MARK H KAPLAN', 18)}}的其他基金
IL-9-dependent interstitial macrophage function in the allergic lung
过敏性肺中 IL-9 依赖性间质巨噬细胞功能
- 批准号:
10741356 - 财政年份:2017
- 资助金额:
$ 23.78万 - 项目类别:
Granzyme A-secreting T cells in allergic inflammation
过敏性炎症中粒酶 A 分泌 T 细胞
- 批准号:
8869766 - 财政年份:2015
- 资助金额:
$ 23.78万 - 项目类别:
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