Defining the epithelial immune response in rhinovirus-triggered pediatric asthma using human nose organoids 9169

Abstract Description Pediatric asthma causes millions of hospitalizations every year and is associated with compromised lung function and multiple comorbidities later in life. Respiratory viruses, primarily human rhinovirus (HRV), are the most common cause of pediatric asthma attacks. Further, epidemiological data suggests early life exposure to rhinovirus induces airway remodeling that precipitates asthma later in childhood. We developed a novel platform of the human airway by culturing basal stem cells isolated non-invasively from the nose into differentiated human nose organoids (HNO). HNO are maintained in an air-liquid interface and reflect the complex cellular heterogeneity observed in the human airway in vivo. We have successfully used the HNO model to examine how rhinovirus infection incites innate antiviral defenses in epithelial cells. We find that asthmatic HNOs have delayed viral clearance, compared to healthy HNOs, in which we observe rapid interferon production that is associated with viral clearance. We propose asthmatic HNOs have an intrinsic defect in their epithelial antiviral immune response. These results are proof-of-concept for an HNO model that recapitulates the asthmatic human airway and can serve as a platform for studying the dysregulated immune response of pediatric asthma to rhinovirus and other respiratory pathogens. Funding Sources Supported by Thrasher Research Fund Early Career Award; Texas Children’s Hospital Pediatrician Scientist Program; NIH AI116497, NIH AI144297. Topic Categories Immediate Hypersensitivity, Asthma, and Allergic Responses (HYP)