The overarching hypothesis of this Program is that the airway epithelium serves as a central coordinator of the responses to respiratory virus infection, and that sensitization to aeroallergens and intrinsic differences in airway epithelial cells (AECs) between asthmatic and healthy individuals is the critical link between exposure and the development of dysfunctional airway responses in asthma. The purpose of Core B ? The Human Airway and Epithelial Cell Culture Core ? is to assist investigators of this Program test this hypothesis using: 1) human airway epithelial cells from carefully characterized asthmatic and healthy children, and 2) airway epithelial cells, endobronchial biopsy samples, and induced sputum samples from well-characterized asthmatic and healthy adults. These primary airway epithelial cells and airway samples from carefully phenotyped human subjects will be used to model interactions between airway epithelial cells and airway stromal cells, extracellular matrix components and leukocytes that regulate the innate and adaptive immune responses to respiratory viruses in the context of allergic sensitization to aeroallergens.
The aims of this Core are to: 1) provide access to primary human airway epithelial cells from well-characterized asthmatic and healthy children, 2) provide access to primary human airway epithelial cells, endobronchial biopsy tissue samples, and induced sputum samples from well-characterized asthmatic and healthy adult subjects, 3) provide the platform to conduct mechanistic experiments utilizing differentiated human airway epithelial cells in organotypic culture, for in vitro studies with lung stromal cells (fibroblasts, airway smooth muscle), and leukocytes to support the aims of the projects proposed in this grant, and 4) extensively phenotype the adults and children enrolled in the core (i.e medical history, pulmonary function, specific allergy testing, and airway hyperresponsiveness) to provide detailed clinical information about the pediatric and adult subjects from whom airway epithelial cells, tissue samples, and sputum samples are isolated to assist in the design, conduct, and analysis of in vitro experiments stratified by the clinical phenotypes and disease severity.
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