Imaging T Cell Airway Responses during Inflammation

炎症期间 T 细胞气道反应的成像

基本信息

批准号：
8239549
负责人：
MATTHEW F KRUMMEL
金额：
$ 32.84万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-04-01 至 2015-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8239549
关键词：
Abbreviations Acute Address Affect Allergens Allergic Alveolar Alveolar Macrophages Antigen Presentation Antigen Targeting Antigen-Presenting Cells Antigens Asthma Attenuated B-Lymphocytes Bacteria Blood Circulation Breathing Bronchi Bronchoalveolar Lavage Bronchus-Associated Lymphoid Tissue CD27 Antigens Cell Communication Cell surface Cells Chronic Dendrites Dendritic Cells Discrimination Disease DsRed Environment Epithelial Eragrostis Feedback Frequencies Goals Green Fluorescent Proteins Guanine Nucleotide Dissociation Inhibitors Hen Egg Lysozyme ITGAX gene IgE Image Imaging Device Immune Immune response Immune system In Vitro Infection Inflammation Inflammatory Inflammatory Response Interleukin-4 Kinetics Label Lead Life Lung Lymphatic Lymphoid Tissue Macrophage Colony-Stimulating Factor Mediastinal Mediating Modeling Mus Mycoplasma Mycoplasma Infections Mycoplasma pulmonis Nature Organ Outcome Ovalbumin Particle Size Particulate Pattern Phagocytosis Phenotype Population Production Reaction Regulation Regulatory T-Lymphocyte Relative (related person)Role Route Sampling Severities Site Structure of parenchyma of lung Surface Surveys Synapses T-Cell Activation T-Cell Receptor T-Lymphocyte T-Lymphocyte Subsets Tissues Transgenes Transgenic Organisms Viral Viral Tumor Antigens airway hyperresponsiveness airway inflammation airway remodeling arginase c-fms Proto-Oncogenes cell motility cytokine immunogenic insight lymph nodes macrophage mast cell mouse langerin mouse model novel particle promoter red fluorescent protein response trafficking uptake

Abbreviations Acute Address Affect Allergens Allergic Alveolar Alveolar Macrophages Antigen Presentation Antigen Targeting Antigen-Presenting Cells Antigens Asthma Attenuated B-Lymphocytes Bacteria Blood Circulation Breathing Bronchi Bronchoalveolar Lavage Bronchus-Associated Lymphoid Tissue CD27 Antigens Cell Communication Cell surface Cells Chronic Dendrites Dendritic Cells Discrimination Disease DsRed Environment Epithelial Eragrostis Feedback Frequencies Goals Green Fluorescent Proteins Guanine Nucleotide Dissociation Inhibitors Hen Egg Lysozyme ITGAX gene IgE Image Imaging Device Immune Immune response Immune system In Vitro Infection Inflammation Inflammatory Inflammatory Response Interleukin-4 Kinetics Label Lead Life Lung Lymphatic Lymphoid Tissue Macrophage Colony-Stimulating Factor Mediastinal Mediating Modeling Mus Mycoplasma Mycoplasma Infections Mycoplasma pulmonis Nature Organ Outcome Ovalbumin Particle Size Particulate Pattern Phagocytosis Phenotype Population Production Reaction Regulation Regulatory T-Lymphocyte Relative (related person)Role Route Sampling Severities Site Structure of parenchyma of lung Surface Surveys Synapses T-Cell Activation T-Cell Receptor T-Lymphocyte T-Lymphocyte Subsets Tissues Transgenes Transgenic Organisms Viral Viral Tumor Antigens airway hyperresponsiveness airway inflammation airway remodeling arginase c-fms Proto-Oncogenes cell motility cytokine immunogenic insight lymph nodes macrophage mast cell mouse langerin mouse model novel particle promoter red fluorescent protein response trafficking uptake

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项目摘要

The lung Is a unique epithelial surface at which inhaled particles, be they inert, bacteria or viral, are trapped in very close proximity to the bloodstream and in a filigree of epithelial surfaces. This presents unique spatial challenges for the T cells of the immune system to properly survey these antigens. Like many epithelial tissues, a selection of Immune macrophage and dendritic cells are poised within and beneath the surface to engulf and either neutralize, or to induce a more profound response to the Insult. During inflammatory insults including those of allergic but also bacterial or viral insults, the lung microenvironment physically changes. This new Project 2 will use live-imaging of viable lung and airways to determine how antigens traffic Into the lung and subsequently activate T cells, focusing the majority of effort upon a mouse model of asthma. The primary Issue being addressed is how inflammatory environments create a feedback loop that promotes accelerated immune responses and thus an enhanced inflammatory environment. We hypothesize that inflammation in the lung airway and aveolae creates a hyperreactive milieu for T lymphocyte priming. This milieu in turn is highly facilltative for synaptic interactions and thus increased production of lung remodeling factors Including cytokines. We propose that there are three distinct components of this. First, that there is a shift in the numbers, localization, antigen uptake and trafficking features between tolerizing phagocytic macrophages and highly immunogenic dendritic cells. The features of inflammatory antigens as well as the features of a remodeled milieu are both proposed to be directly responsible for the shift in the nature of APC which interact with T cells. Second, a shift In local polyclonal and antigen-specific regulatory T cells,modulated in part by the changes in APC population, subsequently modulates the activation of T cells. Finally, that T cells and their APC are modulated by airway remodeling and inflammation induced by agents such as Mycoplasma pulmonis or mast cell depletion. Thus, inflammation creates a fertile stimulatory ground for responses to inhaled antigens.

肺部是一个独特的上皮表面，在该表面上，无论是惰性，细菌还是病毒，都被困在血液中和上皮表面的丝毫之外。这给免疫系统的T细胞带来了独特的空间挑战，可以正确调查这些抗原。像许多上皮组织一样，在表面和下方和树突状细胞的选择中选择了吞噬并吞噬或诱导对侮辱的更深刻反应。在炎症性侮辱中，包括过敏性但细菌或病毒损伤的侮辱，肺微环境在物理上改变。这个新项目2将使用可行的肺和气道的实时成像来确定抗原如何流入肺部并随后激活T细胞，将大部分精力集中在哮喘小鼠模型上。解决的主要问题是炎症环境如何创建反馈回路，从而促进加速的免疫反应，从而增强炎症环境。我们假设肺气道和AVEOLAE中的炎症为T产生了过度反应的环境淋巴细胞启动。反过来，这种环境对突触相互作用具有很高的作用，因此增加了包括细胞因子在内的肺重塑因子的产生。我们建议其中有三个不同的组成部分。首先，数量，定位，抗原摄取和运输特征在耐受性吞噬巨噬细胞和高度免疫原性的树突状细胞之间发生了变化。炎症抗原以及重塑环境的特征都被认为是直接的负责与T细胞相互作用的APC性质的变化。其次，局部多克隆和抗原特异性调节T细胞的变化，部分由APC群体的变化调节，随后调节了T细胞的激活。最后，T细胞及其APC是由诸如支原体肺或肥大细胞耗竭的剂引起的气道重塑和炎症调节的。因此，炎症为对吸入抗原的反应创造了肥沃的刺激基础。