Tissue regulation of T cell function - Reagents Core

T 细胞功能的组织调节 - 试剂核心

• 批准号: 10689177
• 负责人: JIM F Miller
• 金额: $ 31.15万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10689177
• 关键词: Abbreviations; Animal Model; Animals; Antigen-Presenting Cells; Breeding; CD8B1 gene; Calcium; Cell Communication; Cell physiology; Cells; Color; Cues; Cytoskeletal Proteins; Event; Extracellular Matrix; Fluorescence Resonance Energy Transfer; Funding; Gene Expression; Generations; Genetic; Goals; Image; Immune response; Immunologic Memory; Individual; Infection; Inflammatory Response; Integrins; Label; Leukocytes; LoxP-flanked allele; Maintenance; Membrane; Memory; Molecular; Monitor; Mouse Strains; Mus; Myeloid Cells; Peripheral; Population; Positioning Attribute; Process; Proteins; Reagent; Reporter; Research Personnel; Research Project Grants; Retroviridae; Signal Transduction; Site; Structural Protein; T cell regulation; T-Cell Activation; T-Cell Receptor; T-Lymphocyte; Tissues; Transgenic Organisms; cell motility; cell type; effector T cell; experimental study; imaging modality; in vivo imaging; migration; mouse model; multiphoton microscopy; pathogen; programs; recruit; repository; response

PROJECT SUMMARY / ABSTRACT – REAGENT CORE Recruitment and localization of leukocytes to sites of infection in inflamed tissue is a dynamic and regulated process that depends on cross talk between different cell populations, responses to specific environmental cues, and the expression of appropriate effector molecules. The overall goal of this program project is to define key molecular and cellular processes that regulate effective T cell immune responses in peripheral tissue during the initial innate inflammatory response, during effector T cell activation, and during the generation and persistence of tissue-restricted memory. In concordance with this overall goal, the goal of this reagent core is to develop reagents that will enable us to both monitor and manipulate key molecules in a spatially and temporally regulated fashion in specific cell types. The reagents developed in the core will enable all of the projects to probe the functional significance of specific intracellular and membrane-associated events that change as cells interact with other cells and within specific microenvironments in inflamed tissue. The Reagent Core has three aims: 1. To generate retroviruses expressing genetic reporters to image functional events and to manipulate expression of key proteins in T cells. We will generate retroviruses that can be used to localize and manipulate structural proteins that regulate T cell migration and ECM interactions (integrins and cytoskeletal proteins), to monitor intracellular signaling events, and to modify gene expression. 2. To generate and maintain breeding stocks of genetically modified mouse strains that tag specific leukocyte populations with different fluorescent tags. To fully understand how cellular cross talk can influence an immune response, it is necessary to define the cell populations that are present within the inflamed tissue. The goal of this aim will be to maintain a breeding colony of genetically modified mouse lines that express tissue specific fluorescent reporters to identify and distinguish T cells and different myeloid cell populations in inflamed tissue. This repository will enable investigators to “mix and match” fluorescently tagged cells and recipient mice as they plan IV-MPM experiments 3. To create new mouse models to allow for identification and/or manipulation of key leukocyte subpopulations. In this aim we propose to generate several new animal models that are not currently available commercially or collaboratively. These will include mice that express leukocyte subpopulation- specific fluorescent tags, as described in Aim 2 and floxed alleles for integrins (Alpha 1 and Alpha E) that regulate the positioning and function of CD8 TRM cells.

项目摘要 /摘要 - 试剂核心 白细胞在发炎组织中的感染部位募集和定位是一种动态和调节 取决于不同细胞种群之间串扰的过程，对特定环境的响应 提示，以及适当的效应分子的表达。该计划项目的总体目标是 定义关键分子和细胞过程，这些过程调节周围有效T细胞免疫反应 在初始先天炎症反应，效应T细胞激活期间以及期间组织的组织 组织限制记忆的产生和持久性。与这个总体目标一致，目标的目标 试剂核心是开发试剂，使我们能够监测和操纵关键分子 在特定细胞类型中在空间和临时调节时尚。核心中开发的试剂将使 探测特定细胞内和膜相关事件的功能意义的所有项目 当细胞与其他细胞相互作用以及发炎组织中特定的微环境中，这种情况会发生变化。这 试剂芯有三个目标： 1。生成逆转录病毒表达遗传记者以形象功能事件并操纵 T细胞中关键蛋白的表达。我们将生成可用于本地化的逆转录病毒和 操纵调节T细胞迁移和ECM相互作用的结构蛋白（整联蛋白和细胞骨架 蛋白质），监测细胞内信号事件并修饰基因表达。 2。生成和维持遗传修饰的小鼠菌株的繁殖库存 白细胞种群具有不同的荧光标签。充分了解蜂窝交叉说话如何 影响免疫反应，有必要定义存在于 发炎的组织。这个目的的目的是维持基因修饰的小鼠线的繁殖菌落 表达特定组织的荧光记者，以识别和区分T细胞和不同的髓样细胞 发炎组织中的种群。该存储库将使研究人员能够“混合”荧光标记 细胞和受体小鼠计划IV-MPM实验 3。创建新的鼠标模型以识别和/或操纵关键白细胞 亚群。在此目标中，我们建议生成几种当前尚未的新动物模型 商业或协作可用。这些将包括表达白细胞亚群的小鼠 - 特定的荧光标签，如AIM 2中所述，整联蛋白（alpha 1和alpha e）中所述 调节CD8 TRM细胞的定位和功能。