Intelectin 1 Affects Interleukin 13 Induced Mucociliary Airway Dysfunction and Its Expression Is Regulated by a Cis eQTL Associated with Development of Asthma and IBD

RATIONALE Excessive type 2 cytokine airway inflammation is found in∼ 50% of asthmatics and is associated with increased airflow obstruction, likely due to pathologic mucus. We hypothesized that IL-13-induced mucus metaplasia generates an altered apical protein secretome that subsequently modifies mucus properties. To investigate, we characterized the IL-13-induced dysfunction of epithelial mucociliary motion and associated changes in the apical protein secretome. We also utilized CRISPR-knockout to examine the role of Intelectin-1 (ITLN-1) in IL-13-induced mucus pathology. Finally, we used expression quantitative trait loci (eQTL) analysis to identify genetic regulation of ITLN1 and investigated the association with development of asthma and inflammatory bowel disease (IBD). METHODS Human airway epithelial cells (AEC) were obtained from bronchial brushings and tracheal digests, differentiated at …