Function of bronchus-associated macrophages

支气管相关巨噬细胞的功能

• 批准号: 9387774
• 负责人: Christopher David Caballero Allen
• 金额: $ 23.47万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-07 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9387774
• 关键词: Affect; Allergens; Allergic; Allergic inflammation; Alveolar Macrophages; Antigen-Presenting Cells; Asthma; Breathing; Bronchi; Bronchial Tree; CD4 Positive T Lymphocytes; Cells; Child; Controlled Study; Dendritic Cells; Disease; Distal; Goals; Individual; Inflammation; Inflammatory Response; Lung; Lung Inflammation; Lung diseases; MHC Class II Genes; Molecular; Morphology; Pathogenesis; Phenotype; Play; Population; Prevalence; Pulmonary Pathology; Role; Symptoms; adaptive immune response; asthmatic; insight; macrophage; mouse model; respiratory smooth muscle; response; uptake

Project Summary/Abstract Asthma is a lung disease that is growing in prevalence and disproportionately affects children. Many asthmatics show underlying allergic inflammation that is thought to trigger their symptoms, and suppressing inflammation shows efficacy in treating disease. However, the mechanism by which allergen inhaled into the lung actually initiates inflammatory responses is poorly understood. In particular, the allergen must be taken up by so-called professional antigen presenting cells to be presented to CD4 T cells, yet the uptake of allergen from the airway lumen has not been well characterized. In preliminary studies, we have identified a subset of macrophages which appear to be the main allergen capturing cells near the bronchi, where inflammation develops. These bronchus-associated macrophages are phenotypically distinct from alveolar macrophages in the distal airways as well as from classical dendritic cells. The overall goal of this proposal is to determine whether bronchus-associated macrophages are important for the allergic inflammation near the bronchial tree. The specific aims are to 1) characterize the distinct features and cellular interactions of bronchus-associated macrophages compared with classical dendritic cells and 2) assess the impact of deficiency in bronchus- associated macrophages on allergic lung inflammation. We believe these studies will provide important new insights into the mechanism by which allergen is taken up from the bronchi in the initiation of allergic lung inflammation, which may have important implications for understanding the pathogenesis of asthma.

项目摘要/摘要 哮喘是一种肺部疾病，患病率正在增长，对儿童的影响不成比例。许多 哮喘患者显示出潜在的过敏性炎症，这些炎症被认为会触发其症状并抑制 炎症显示出治疗疾病的功效。但是，过敏原吸入的机制 肺实际上发起炎症反应的理解很少。特别是，必须服用过敏原 通过所谓的专业抗原呈现细胞，要呈现给CD4 T细胞，但过敏原的摄取 从气道管腔尚未得到很好的特征。在初步研究中，我们确定了一个子集 巨噬细胞似乎是支气管附近的主要过敏原捕获细胞，炎症 发展。这些与支气管相关的巨噬细胞在表型上与肺泡巨噬细胞不同 远端气道以及经典的树突状细胞。该提议的总体目标是确定 与支气管相关的巨噬细胞是否对支气管树附近的过敏性炎症很重要。 具体目的是1）表征与支气管相关的不同特征和细胞相互作用 与经典的树突状细胞相比，巨噬细胞和2）评估支气管缺乏的影响 在过敏性肺部炎症上相关的巨噬细胞。我们认为这些研究将提供重要的新 对过敏性肺部从支气管中服用过敏原的机制的见解 炎症，这可能对理解哮喘的发病机理具有重要意义。