Function of bronchus-associated macrophages

项目摘要/摘要 哮喘是一种发病率越来越高的肺部疾病，对儿童的影响不成比例。许多 哮喘患者表现出潜在的过敏性炎症，被认为是引发他们症状的原因，并抑制了 炎症在治疗疾病中显示出疗效。然而，过敏原吸入人体的机制 肺实际上启动了炎症反应，但人们对此知之甚少。特别是，必须服用过敏原。 由所谓的专业抗原提呈细胞提呈给CD4T细胞，但摄取变应原 来自气道腔的特征尚未得到很好的描述。在初步研究中，我们已经确定了 巨噬细胞似乎是主要的过敏原，捕获支气管附近的细胞，在那里炎症 发展起来。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 远端呼吸道和经典树突状细胞。这项提案的总体目标是确定 支气管相关巨噬细胞在支气管树附近的过敏性炎症中是否起重要作用。 其具体目的是1)描述与支气管相关的不同特征和细胞间的相互作用 巨噬细胞与经典树突状细胞的比较以及2)评估支气管缺乏的影响- 相关巨噬细胞在过敏性肺部炎症中的作用。我们相信这些研究将提供重要的新的 从支气管摄取变应原引发变态反应性肺的机制 炎症，这可能对理解哮喘的发病机制有重要意义。

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.