Integrins αvβ5 and αvβ6 Mediate IL-4–induced Collective Migration in Human Airway Epithelial Cells

A positive link between persistent cellular motion and a defective tight junction barrier allows increased antigenic penetration and contact between ligand–receptor pairs, leading to exacerbated allergic airway inflammation and remodeling. Given that collective cell migration involves cell–cell and cell–extracellular matrix adhesions, and given that IL-4 induces epithelial barrier dysfunction and decreases cell–extracellular matrix adhesions, we hypothesized that IL-4 may induce collective migration in the well-differentiated primary human nasal epithelial cells (HNECs). Well-differentiated HNECs were treated with IL-4, and the effects of IL-4 on cell migration were investigated using genetic and pharmacological approaches, live-cell imaging, a vertex model, and immunostaining. IL-4 disrupted the expression and localization of the tight junction proteins zonula occludens 1 and occludin, and it induced the cleavage and asymmetric distribution of E-cadherin in the HNEC layers. It also induced collective epi...