Defining a type II IL-9R

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的表达使我们对IL-9如何向非造血细胞传递信号的了解存在空白。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。

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.