Function of bronchus-associated macrophages

项目概要/摘要 哮喘是一种肺部疾病，患病率不断上升，对儿童的影响尤为严重。许多 哮喘患者表现出潜在的过敏性炎症，这被认为是引发他们的症状， 炎症显示出治疗疾病的功效。然而，过敏原被吸入皮肤的机制， 肺实际上引发炎症反应的机制知之甚少。特别是，过敏原必须采取了 由所谓的专职抗原呈递细胞呈递给CD 4 T细胞，但过敏原的摄取 还没有很好地表征。在初步研究中，我们已经确定了一个子集， 巨噬细胞似乎是主要的过敏原捕获细胞附近的支气管，炎症 发展起来的这些支气管相关巨噬细胞在表型上不同于肺泡巨噬细胞， 远端气道以及经典的树突状细胞。本提案的总体目标是确定 支气管相关巨噬细胞是否对支气管树附近的过敏性炎症很重要。 具体目标是：1）表征支气管相关性哮喘的独特特征和细胞相互作用， 巨噬细胞与经典树突状细胞的比较和2）评估支气管- 相关巨噬细胞对过敏性肺部炎症的影响。我们相信这些研究将提供重要的新的 了解过敏原从支气管摄取引发过敏性肺的机制 炎症，这可能对理解哮喘的发病机制具有重要意义。

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.