Airways Eosinophils as Antigen-presenting Cells in Asthma

气道嗜酸性粒细胞作为哮喘中的抗原呈递细胞

基本信息

批准号：
7921759
负责人：
PETER F WELLER
金额：
$ 29.12万
依托单位：
BETH ISRAEL DEACONESS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-17 至 2011-09-16
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7921759
关键词：
Abbreviations Allergens Allergic Antibodies Antigen Presentation Antigen-Presenting Cells Antigens Asthma B-Lymphocytes Bronchoalveolar Lavage Cell Communication Cell physiology Cells Cessation of life Chronic Cytoplasmic Granules Dendritic Cells Disease Eicosanoids Electron Microscopy Eotaxin Erythrocytes Fc Receptor Hen Egg Lysozyme Human IgE IgG Receptors Immune Immunization Immunoglobulin A Immunoglobulin G Inflammation Inflammation Mediators Knock-out Leukocytes Leukotriene C4 Ligands Lung Lymphocyte Lymphocyte antigen CD50 Lymphoid Lymphoid Cell Lymphoid Tissue MHC Class II Genes Mediating Mediation Mus Myelogenous Nature Organ Ovalbumin Paratracheal Participant Process Proteins Public Health Receptors, Antigen, B-Cell Recruitment Activity Regulation Research Respiratory System Respiratory tract structure Role SLAM protein Site Spleen Sputum Staging Structure of thyroid parafollicular cell Synapses T-Cell Receptor T-Lymphocyte TSLP gene Testing Thymus Gland Transgenic Organisms Transport Process allergic airway disease aluminum sulfate base cysteinyl-leukotriene cytokine eosinophil eosinophil peroxidase gastrointestinal human TSLP protein in vivo insight intraperitoneal lymph nodes novel paracrine programs public health relevance receptor response trafficking

项目摘要

DESCRIPTION (provided by applicant): Studies will investigate capabilities and mechanisms whereby eosinophils, including those recruited within airways in asthma, function as antigen-presenting cells that are of importance in propagating or modulating varied lymphocyte-dependent responses to respiratory tract encountered antigens. As antigen-presenting cells, eosinophils have distinct capabilities: First, airway eosinophils express requisite Class II MHC and lymphocyte costimulatory proteins. Second, eosinophils, like dendritic cells, function as "professional" antigen-presenting cells in expressing lymphocyte costimulatory proteins and activating unsensitized, naive T cells. Third, eosinophils, in contrast to other antigen-presenting cells, contain preformed stores of diverse cytokines that can be rapidly and selectively secreted to modulate varied lymphocyte responses. Fourth, eosinophils, like other antigen-presenting cells, utilize Fc receptor- mediated mechanisms to enhance antigen presentation by antigen-presenting cells. Eosinophil IgE, IgA and IgG receptors, together with airway allergen-specific IgE, IgA and IgG antibodies, can effectively present allergens. Fifth, airway eosinophils traffick into lymph nodes, spleen and even the thymus enabling airway antigens to be processed and transported into regional and systemic lymphoid tissues for presentation to varied lymphocytes. Sixth, eosinophils express ligands and receptors classically associated with dendritic cells, including DC-SIGN. Moreover, eosinophils can modulate B lymphocyte responses since eosinophils are critical participants in alum immunization-mediated B cell priming. Hypotheses to be tested are: that eosinophils trafficking from the airways are effective at presenting antigens to regulate, potentially differing, T lymphocyte responses in both regional and systemic lymphoid cells; that selective, restricted secretion of eosinophil cytokines mediates differential regulation of eosinophil antigen-presenting cell functions; and that eosinophils have roles in mediating the priming and responsiveness of B cells. Studies aim to investigate mechanisms by which eosinophils traffic and function as antigen-presenting cells to regulate regional and systemic T cell responses; eosinophil cytokines function in differential mediation of eosinophil antigen-presenting cell functions, and eosinophils function in B cell priming and activation. Roles for eosinophils as antigen-presenting cells in mediating allergic responses to airway antigens would provide novel insights into the characteristically chronic nature of asthma and other allergic airway diseases. PUBLIC HEALTH RELEVANCE. Asthma is an increasingly prevalent disease and a major public health problem. The research will help in understanding mechanisms that contribute to making asthma a chronic and persistent disease.

描述（由申请人提供）：研究将调查嗜酸性粒细胞（包括哮喘气道内招募的嗜酸性粒细胞）作为抗原呈递细胞发挥作用的能力和机制，这些细胞对于传播或调节对呼吸道遇到的抗原的各种淋巴细胞依赖性反应至关重要。作为抗原呈递细胞，嗜酸性粒细胞具有独特的功能：首先，气道嗜酸性粒细胞表达必需的 II 类 MHC 和淋巴细胞共刺激蛋白。其次，嗜酸性粒细胞与树突状细胞一样，在表达淋巴细胞共刺激蛋白和激活未致敏的初始 T 细胞方面充当“专业”抗原呈递细胞。第三，与其他抗原呈递细胞相比，嗜酸性粒细胞含有预先储存的多种细胞因子，可以快速、选择性地分泌这些细胞因子来调节不同的淋巴细胞反应。第四，嗜酸性粒细胞与其他抗原呈递细胞一样，利用Fc受体介导的机制来增强抗原呈递细胞的抗原呈递。嗜酸性粒细胞IgE、IgA和IgG受体与气道过敏原特异性IgE、IgA和IgG抗体一起可以有效呈递过敏原。第五，气道嗜酸性粒细胞流入淋巴结、脾脏甚至胸腺，使气道抗原能够被加工并转运到区域和全身淋巴组织中，以呈递给各种淋巴细胞。第六，嗜酸性粒细胞表达通常与树突状细胞相关的配体和受体，包括DC-SIGN。此外，嗜酸性粒细胞可以调节 B 淋巴细胞反应，因为嗜酸性粒细胞是明矾免疫介导的 B 细胞启动的关键参与者。需要测试的假设是：来自气道的嗜酸性粒细胞能够有效地呈递抗原，以调节区域和全身淋巴细胞中可能存在差异的 T 淋巴细胞反应；嗜酸性粒细胞细胞因子的选择性、限制性分泌介导嗜酸性粒细胞抗原呈递细胞功能的差异调节；嗜酸性粒细胞在介导 B 细胞的启动和反应中发挥作用。研究旨在调查嗜酸性粒细胞作为抗原呈递细胞运输和发挥作用以调节区域和全身 T 细胞反应的机制；嗜酸性粒细胞细胞因子在嗜酸性粒细胞抗原呈递细胞功能的差异介导中发挥作用，而嗜酸性粒细胞在B细胞启动和激活中发挥作用。嗜酸性粒细胞作为抗原呈递细胞在介导气道抗原过敏反应中的作用将为了解哮喘和其他过敏性气道疾病的慢性特征提供新的见解。公共卫生相关性。哮喘是一种日益流行的疾病，也是一个重大的公共卫生问题。该研究将有助于了解导致哮喘成为慢性持续性疾病的机制。