The role of IL-7/IL7R interactions in the development, maintenance and organization of the lymph node microenvironment.

IL-7/IL7R 相互作用在淋巴结微环境的发育、维持和组织中的作用。

• 批准号: G0601156/1
• 负责人: Mark Coles
• 金额: $ 50.44万
• 依托单位: University of York
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0601156%2F1
• 关键词: role; IL; IL7R; interactions; development

The lymph node or ?gland? is a dynamic microenvironment of lymphocytes, dendritic cells and lymph node stromal cells where immune responses are initiated. Intercellular interactions between these cells are essential for the survival, homeostasis and function of all of these cell types, with disruption of these interactions leading to cell death. In order to study the involvement of locally produced cytokines (immune hormones) in the interdependency of these different cells we propose to generate mice in which lymph node stromal cells expressing cytokines are tagged by fluorescent proteins. The homeostasis of peripheral T cells is dependent on IL-7 which is produced by lymph node stromal cells. To visualize stromal cells we will generate IL-7 fluorescent protein mice. Utilizing multiphoton microscopy, tissue culture, gene expression analysis and flow cytometry we will analyze the molecular and cell biology of lymphocyte - stromal cell interactions during lymph node development, homeostasis and organization. Our experiments will test the hypothesis that IL-7/IL7R interactions between stromal cells and lymphocytes are required for the development of the lymph node microenvironment.The main objectives of our proposal are:i) To characterize lymph node stromal cell biology.ii) To examine the role of IL-7/IL7R interactions in the development, organization and maintenance of the lymph node microenvironment.iii) To characterize the molecular mechanism governing intercellular communication initiated by IL-7/IL7R signalling between lymphocytes and lymph node stromal cells.

是淋巴结还是腺体？是启动免疫反应的淋巴细胞、树突状细胞和淋巴结基质细胞的动态微环境。这些细胞之间的细胞间相互作用对于所有这些细胞类型的生存、内稳态和功能都是必不可少的，这些相互作用的破坏会导致细胞死亡。为了研究局部产生的细胞因子(免疫激素)在这些不同细胞的相互依赖中的作用，我们建议用荧光蛋白标记表达细胞因子的淋巴结基质细胞的小鼠。外周T细胞的动态平衡依赖于由淋巴结基质细胞产生的IL-7。为了使基质细胞可视化，我们将产生IL-7荧光蛋白小鼠。利用多光子显微镜、组织培养、基因表达分析和流式细胞术，我们将分析淋巴-基质细胞在淋巴结发育、动态平衡和组织过程中相互作用的分子和细胞生物学。我们的实验将验证这一假设，即基质细胞和淋巴细胞之间的IL-7/IL7R相互作用是淋巴结微环境发育所必需的。我们建议的主要目标是：i)研究淋巴结基质细胞的生物学特性。ii)研究IL-7/IL7R相互作用在淋巴结微环境的发展、组织和维持中的作用。iii)表征由IL-7/IL7R信号在淋巴细胞和淋巴结基质细胞之间启动的细胞间通讯的分子机制。