Molecular Regulation of Cytokine Responsiveness in CD4+ T Cells

CD4 T 细胞细胞因子反应性的分子调控

• 批准号: 418675-2013
• 负责人: PeronaWright, Georgia
• 金额: $ 2.99万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=573783
• 关键词: Molecular; Regulation; Cytokine; Responsiveness; CD4+

The disparate cell populations of the immune system are orchestrated by a family of secreted signal-ling molecules known as cytokines. Cytokines influence the size, speed and quality of an immune re-sponse. They signal via specific receptors on the surface of target cells, and their impact is determined both by the amount of cytokine made and by the ability of the target cell to respond. My overall research goal is to determine how cytokine signalling can be exploited in order to enforce a particular quality of immune response. The aim of this research program is to understand how changes in cytokine receptor expression affect the activation and differentiation of a particular type of immune cell, the CD4+ helper T cell. Helper T cells are a regulatory cell population and a potent source of both pro- and anti- inflam-matory mediators. Our central hypothesis is that changes in cytokine responsiveness are inherent to helper T cell differentiation and dictate the function of these cells during a recall response. Our specific objectives in the first five year period are to determine the impact of changes in cytokine receptor ex-pression on the function of helper T cells, to identify the mechanisms by which cytokine receptor ex-pression is controlled, and to assess the interaction between different cytokine receptors on the T cell surface. We will test a model in which the impact of cytokine signalling is controlled not by the source but by the target cell. The work is expected to elucidate a new aspect of helper T cell differentiation, in which progressive modulation of a cell's cytokine receptor repertoire dictates the cell's functional poten-tial. The studies address fundamental questions of signal control, cell differentiation and fate commit-ment, and the knowledge to be generated is therefore of broad biological interest. A molecular under-standing of the control of cytokine signalling is also an important step toward the development of new biotechnologies that manipulate cellular communication, and this research thus represents both intellec-tual and economic investment for Canada.

免疫系统中不同的细胞群是由一个被称为细胞因子的分泌信号分子家族协调的。细胞因子影响免疫应答的大小、速度和质量。它们通过靶细胞表面的特异性受体发出信号，其影响由产生的细胞因子的量和靶细胞的反应能力决定。我的总体研究目标是确定如何利用细胞因子信号传导来加强免疫反应的特定质量。该研究计划的目的是了解细胞因子受体表达的变化如何影响特定类型免疫细胞（CD4+辅助T细胞）的活化和分化。辅助性T细胞是一种调节性细胞群，是促炎和抗炎介质的有效来源。我们的中心假设是，细胞因子反应性的变化是固有的辅助T细胞分化，并决定这些细胞在回忆反应的功能。我们在前五年的具体目标是确定细胞因子受体表达的变化对辅助性T细胞功能的影响，以确定细胞因子受体表达的控制机制，并评估T细胞表面不同细胞因子受体之间的相互作用。我们将测试一个模型，其中细胞因子信号传导的影响不是由来源控制，而是由靶细胞控制。这项工作有望阐明辅助性T细胞分化的一个新方面，其中细胞因子受体库的渐进调节决定了细胞的功能潜力。这些研究解决了信号控制、细胞分化和命运决定的基本问题，因此产生的知识具有广泛的生物学意义。细胞因子信号控制的分子理解也是操纵细胞通讯的新生物技术发展的重要一步，因此这项研究代表了加拿大的智力和经济投资。