Efficacy of IgE in Mediating Allergic Reactions in Vivo

IgE 在介导体内过敏反应中的功效

• 批准号: 7487023
• 负责人: Donald W MacGlashan
• 金额: $ 113.08万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7487023
• 关键词: Efficacy; IgE; Mediating; Allergic; Reactions; Efficacy; IgE; Mediating; Allergic; Reactions

DESCRIPTION (provided by applicant): The central element in allergic diseases such as asthma, rhinitis and eczema, is the presence of IgE antibody. While there is general acceptance of the central role for IgE in these diseases, there remains only a poor understanding of the quantitative requirements for IgE in the expression of these diseases. This application focuses on obtaining better quantitative insights on several aspects of the problem. In project by Bochner, two underlying hypotheses are examined, 1) that it is the ratio of antigen-specific IgE to total IgE that is a critical determinant of an in vivo response to allergen challenge and 2) that mast cells are a central determinant in early tissue localized reactions like those in the nose while basophils are involved in food reactions where antigen exposure is likely to occur in the blood. Project 2 offers an extended hypothesis for critical parameters, that not only is the specific to total IgE ratio important, but cellular sensitivity (the quantitative assessment of a cell's ability to respond to antigen) also defines the response. Other aims in project by Macglashan address issues of FceRI expression, how the beta subunit of this receptor is controlled and its influence on overall expression of FceRI and how other early signaling molecule expression is regulated by IgE antibody. A common theme in these studies as well as a theme that binds the various projects together is that the regulation is quantitatively different in vivo than in vitro and we will be assessing these differences and how they influence our understanding of disease expression. In one respect, project by Shroeder re-examines quantitative aspects of basophil and mast cell responses. While staying with the theme of IgE centrality, Project 3 examines the FceRI-bearing antigen-presenting cells and the interaction of FceRI and innate immune receptors. Aims in this project will examine how changes in IgE antibody alter expression of FceRI on dendritic cells and whether this results in changes in the expression and profile of cytokines elaborated by these cells. Changes in the expression and function of innate receptors on dendritic cells and basophils will also be a focus of this project. Finally, this project will examine the influence of IgE on the systemic effects of large local reactions by examining various parameters of basophil and dendritic cell function following in vivo manipulation of IgE and experimental antigen exposure. All projects will modulate IgE levels in vivo to make quantitative determinations of the effects these changes have on various outcomes associated with allergic diseases. Beyond the required administrative core (A), there are two scientific Cores. The Subject Characterization and Recruitment Core provides the comprehensive subject recruitment and characterization that is required for all three projects. The Diagnostics Core provides the comprehensive diagnostic and laboratory assays needed for all three projects.

描述（由申请人提供）： 过敏性疾病（例如哮喘，鼻炎和湿疹）的中心因素是IgE抗体的存在。尽管普遍接受IgE在这些疾病中的核心作用，但对这些疾病表达中IgE的定量要求仍然存在很差的理解。该应用程序着重于对问题的几个方面获​​得更好的定量见解。在Bochner的项目中，研究了两个潜在的假设，1）是，抗原特异性IgE与总IgE的比率是对体内对过敏原挑战的反应的关键决定因素，而2）肥大细胞在早期的组织局部反应中是鼻子中的核心局部反应，例如鼻子中的植物反应，在植物反应中可能与植物反应相关。项目2为关键参数提供了扩展的假设，不仅特定于总IgE比率很重要，而且细胞敏感性（对细胞对抗原响应抗原响应能力的定量评估）也定义了响应。 MacGlashan在项目中的其他目的解决了FCERI表达的问题，该受体的β亚基如何受到控制以及其对FCERI的总体表达的影响以及其他早期信号分子表达如何受IgE抗体的调节。这些研究中的一个共同主题以及将各个项目绑定在一起的主题是，体内的调节在定量上与体外有所不同，我们将评估这些差异以及它们如何影响我们对疾病表达的理解。在一个方面，shroeder重新检查嗜碱性粒细胞和肥大细胞反应的定量方面的项目。在以IgE中心性为主题的同时，Project 3研究了含有FCERI的抗原呈递细胞以及FCERI和先天免疫受体的相互作用。该项目的目的将研究IgE抗体的变化如何改变树突状细胞上FCERI的表达，以及这是否导致这些细胞阐述的细胞因子的表达和曲线变化。先天受体在树突状细胞和嗜碱性粒细胞上的表达和功能的变化也将是该项目的重点。最后，该项目将通过检查嗜碱性粒细胞和树突状细胞功能的各种参数在体内操纵IgE和实验抗原暴露后检查IgE对大型局部反应的系统影响的影响。所有项目都将在体内调节IGE水平，以定量确定这些变化对与过敏性疾病相关的各种结果的影响。除了所需的行政核心（a）之外，还有两个科学核心。主题表征和招聘核心提供了所有三个项目所需的全面招聘和表征。诊断核心提供了所有三个项目所需的全面诊断和实验室测定。