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Tissue regulation of T cell function

T 细胞功能的组织调节

基本信息

批准号：
9491663
负责人：
Deborah J Fowell
金额：
$ 164.34万
依托单位：
UNIVERSITY OF ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-06-01 至 2019-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9491663
关键词：
Address Allergic Antigen-Presenting Cells Antigens Architecture Autoimmune Process Autoimmunity Basement membrane Binding Biological CD8-Positive T-Lymphocytes Cardiovascular Diseases Cell Communication Cell physiology Cells Chronic Communities Complex Cues Cytolysis Data Development Educational workshop Effector Cell Environment Epithelial Cells Epithelium Extracellular Matrix Generations Goals Homing Image Image Analysis Imagery Immune response Immunity In Situ Infection Inflammation Inflammatory Inflammatory Response Influenza Integrins Knowledge Leukocytes Location Lung Lymphoid Tissue Mediating Mediator of activation protein Memory Microscopy Molecular Mucous Membrane Mus Pathogenicity Process Regulation Research Personnel Shapes Signal Transduction Site Skin Skin Tissue Specificity Structure of parenchyma of lung Surveys System T cell regulation T memory cell T-Lymphocyte Time Tissues Virus base cell motility chemokine combinatorial cytokine cytotoxic design flexibility imaging approach immune activation immunological diversity in vivo in vivo imaging inflammatory milieu innovation insight interstitial intravital imaging lymph nodes meetings migration neutrophil novel pathogen programs recruit response secondary infection symposium targeted treatment tool

项目摘要

DESCRIPTION (provided by applicant): Many pathogens enter and reside in barrier tissues of the skin and lung. Pathogen control ultimately requires the recruitment and activation of immune effectors to specific infected tissue micro-environments. While we have gained much insight into effector T cell generation in lymphoid tissues there exists a significant knowledge gap on the fate of effector T cells once they leave the lymph node. Yet it is within the inflamed tissue milieu that T cells must mediate their effector functions, including cytokine secretion and cytolysis, to clear the infection. The central hypothesis is that the specific tissue and the local inflammatory milieu will shape T cell recruitment and effector function. Such tissue-control is likely to impact the magnitude and functional diversity of the immune response. Optimizing T cell function in tissues is critical for pathogen clearance and the avoidance of collateral damage. The goal of this proposal is to define the checkpoints and identify molecular interactions that guide successful immunity at sites of inflammation. The objective of this Program Project is to bring together scientific expertise in migration and effector function to address fundamental effector T cell processes in infected tissues using cutting-edge intra-vital imaging approaches. When effector T cells enter the inflamed tissue they encounter a tissue environment that has been differentially altered depending on the type of pathogen and corresponding inflammation. The ability of T cells sense and interpret different inflammatory environments and the impact on effective pathogen clearance are poorly understood. Project 1 (Dr. Minsoo Kim) addresses how neutrophils modify the micro-environment and how T cells integrate multiple tissue-specific inflammatory cues. Project 2 (Dr. Deborah Fowell) determines how the altered milieu controls the mechanisms used by effector T cells to migrate and survey the tissue for antigen-bearing APC/infected cells. Project 3 (Dr. David Topham) focuses on how the inflamed lung tissue modifies CDS migration and impacts on the development of long-term tissue memory to influenza infection. These processes are critical to the clearance of pathogens but also support the activation of immunity in chronic inflammation, autoimmune and allergic settings. Using innovative tools for in situ modulation and visualization of immune responses in the skin and lung we will define the molecular parameters for effector T cell movement and function at distinct sites of inflammation.

描述（由申请人提供）：许多病原体进入并驻留在皮肤和肺部的屏障组织中。病原体控制最终需要招募和激活免疫效应器到特定的感染组织微环境。虽然我们已经对淋巴组织中效应T细胞的产生有了深入的了解，但在效应T细胞离开淋巴结后的命运方面存在着重大的知识差距。然而，正是在炎症组织环境中，T细胞必须调节其效应功能，包括细胞因子分泌和细胞溶解，以清除感染。中心假设是特定组织和局部炎症环境将塑造T细胞募集和效应功能。这种组织控制可能会产生影响