B cell antigen presentation in chronic allergic lung disease (asthma)

描述(申请人提供)：近几十年来，哮喘在美国和其他工业化国家的患病率急剧上升。慢性过敏性肺病(过敏性哮喘)占哮喘的大部分。大量研究表明，Th2细胞和Th2细胞因子包括IL-4、IL-5和IL-13在变态反应性肺部疾病及其下游事件的发生发展中发挥重要作用，包括炎症、嗜酸性粒细胞增多、肥大细胞聚集/激活和气道重塑。然而，影响Th2细胞发育和维持的机制却知之甚少。初始T细胞的增殖和分化是由与携带同源抗原的抗原提呈细胞相互作用而触发的。越来越清楚的是，这种相互作用周围的条件会影响T细胞分化。这项建议将调查B细胞在慢性过敏性肺部疾病期间塑造T细胞反应中的作用。此外，还将研究重要的先天分子在调节B细胞抗原提呈中的作用。在这些研究中，我们研究了B细胞在慢性变态反应性肺部疾病中的作用，重点是B细胞作为抗原提呈细胞的作用。这些特定的目的将为研究B细胞在变态反应性疾病中的作用奠定基础，但这些研究将对理解B细胞在其他慢性疾病的免疫学中的作用具有相关性。 相关性：慢性过敏性肺病(哮喘)的特征是免疫系统的不适当激活。B细胞是导致这种疾病和其他慢性疾病的重要因素。这个项目的重点是B细胞在维持变态反应性疾病中的作用，但也将深入了解B细胞如何在各种其他疾病中促进耐受和免疫激活的平衡。

DESCRIPTION (provided by applicant): In recent decades, the prevalence of asthma in the US and other industrialized countries has increased dramatically. Chronic allergic lung disease (allergic asthma) accounts for a majority of asthma. Many studies have demonstrated that Th2 cells and Th2 cytokines including IL-4, IL-5, and IL-13 play an important role in the development of allergic lung disease and the downstream events, including inflammation, eosinophilia, mast cell accumulation/activation, and airway remodeling. However, less is known about the mechanisms that affect the development and maintenance of Th2 cells. The proliferation and differentiation of naive T cells is triggered by interactions with antigen presenting cells bearing cognate antigen. It is becoming increasing clear that the conditions surrounding this interaction influence T cell differentiation. This proposal will investigate the role that B cells have in shaping the T cell response during chronic allergic lung disease. In addition, the role of important innate molecules will be investigated for their contribution to the regulation of B cell antigen presentation. In these studies, we investigate the role of B cells in chronic allergic lung disease, with an emphasis on the role of B cells as antigen presenting cells. These specific aims will build a foundation for investigating the role of B cells in allergic disease, but these studies will have relevance for understanding the role of B cells in the immunology of other chronic diseases. RELEVANCE: Chronic allergic lung disease (asthma) is characterized by inappropriate activation of the immune system. B cells are a significant contributor to this and other chronic diseases. This project focuses on the role of B cells in perpetuating allergic disease, but will give insights into how B cells contribute to the balance of tolerance versus immune activation in a variety of other diseases, as well.