Dendritic cells and IgE in asthma

哮喘中的树突状细胞和 IgE

• 批准号: 7368057
• 负责人: Mark C Liu
• 金额: $ 38.14万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7368057
• 关键词: Affinity; Allergens; Allergic; Antigen-Presenting Cells; Antigens; Asthma; Basophils; Blood; Bone Marrow Myeloid Stem Cell; CD4 Positive T Lymphocytes; Cell Differentiation process; Cell Maturation; Cell physiology; Cells; Chronic; Data; Dendritic Cells; Disease; Environment; Epithelium; Equilibrium; Event; Extrinsic asthma; Helper-Inducer T-Lymphocyte; Human; IgE; IgE Receptors; Immune response; Immunity; Immunologics; In Vitro; Individual; Inflammation; Inflammatory; Kinetics; Link; Localized; Lung; Lymphoid Cell; Lymphoid Tissue; Mediating; Modeling; Myelogenous; Neurons; Neuropilin-1; Numbers; Oligonucleotides; Phenotype; Play; Production; Recruitment Activity; Research Personnel; Role; Role playing therapy; Site; Stimulus; Surface; T memory cell; T-Cell Proliferation; T-Lymphocyte; Testing; Tetanus Toxoid; Tissues; atopy; base; chemokine; chemokine receptor; cytokine; eosinophil; human study; human subject; in vivo; insight; mast cell; monocyte; novel; omalizumab; programs; receptor; receptor expression; response

DESCRIPTION: Asthma is an airways disease characterized by a unique form of chronic inflammation associated with a profile of cytokines produced by the Th2-subset of helper T lymphocytes. Asthma is most often associated with atopy, allergen sensitization, and the IgE response, which are also regulated by Th2 cytokines. Using the human model of segmental allergen challenge (SAC), specific recruitment of eosinophils, basophils, and helper/memory T lymphocytes has been demonstrated, suggesting highly selective mechanisms of cellular recruitment. Our novel preliminary data indicates that dendritic cells (DCs) rapidly accumulate at sites of SAC in numbers sufficient to allow examination of their function. This proposal will examine the role of dendritic cells in the inflammatory and immunologic response to allergen. We will examine the hypothesis that early in the allergic response, DCs accumulate in the lung by direct recruitment or by differentiation from circulating monocyte precursors. By altering the balance of antigen presenting cell (APC) function, lung DCs play a critical role in localizing immune responses to the inflammatory site. Our approaches are as follows 1) We will examine the kinetics of myeloid and plasmacytoid DC recruitment to the lung, and identify the chemokines involved in lung DC recruitment. 2) Using purified DC subsets and CD4+ T cells, we will perform functional studies of lung DCs to define changes in ARC functions and DC cytokine production associated with recruitment to the lung. 3) We will evaluate the expression of high affinity IgE receptor (Fcc.RI) on lung DCs during inflammation, and explore the role of IgE-mediated mechanisms on DC function. In vitro studies will examine the effect on DC function of modulating IgE with a non-activating, anti-lgE (omalizumab) and other stimuli. Better understanding of DC recruitment, function, and the role of IgE may provide insight into strategies aimed at restoring balance to the dysregulated immune response in the airways associated with allergic asthma.

产品说明：哮喘是一种气道疾病，其特征在于与辅助性T淋巴细胞的Th 2亚群产生的细胞因子谱相关的独特形式的慢性炎症。 哮喘最常与特应性、过敏原致敏和IgE反应相关，这些反应也受Th 2细胞因子调节。 使用节段性过敏原攻击（SAC）的人类模型，嗜酸性粒细胞，嗜碱性粒细胞和辅助/记忆T淋巴细胞的特异性募集已被证明，表明细胞募集的高度选择性机制。 我们的新的初步数据表明，树突状细胞（DC）迅速积累在SAC的网站数量足以让他们的功能检查。 本研究将探讨树突状细胞在过敏原的炎症和免疫反应中的作用。 我们将研究这一假设，即在过敏反应的早期，DCs通过直接募集或从循环单核细胞前体分化而在肺中积累。 通过改变抗原呈递细胞（APC）功能的平衡，肺DC在将免疫应答定位于炎症部位中起关键作用。 我们的方法如下：1）我们将检查髓样和浆细胞样DC向肺募集的动力学，并鉴定参与肺DC募集的趋化因子。2)使用纯化的DC亚群和CD 4 + T细胞，我们将进行肺DC的功能研究，以确定ARC功能和DC细胞因子产生与肺募集相关的变化。3)我们将评估高亲和力IgE受体（Fcc.RI）在炎症过程中肺DC上的表达，并探讨IgE介导的机制对DC功能的作用。 体外研究将检查用非活化的抗IgE（奥马珠单抗）和其他刺激物调节IgE对DC功能的影响。 更好地了解DC的募集，功能和IgE的作用，可以提供深入了解旨在恢复与过敏性哮喘相关的气道免疫反应失调的平衡的策略。