Airway epithelial cells as drivers of severe asthma pathogenesis.

Our understanding of the airway epithelium's role in driving asthma pathogenesis has evolved over time. From being regarded primarily as a physical barrier that could be damaged via inflammation, the epithelium is now known to actively contribute to asthma development through interactions with the immune system. The airway epithelium contains multiple cell types with specialized functions spanning barrier action, mucociliary clearance, immune cell recruitment, and maintenance of tissue homeostasis. Environmental insults may cause direct or indirect injury to the epithelium leading to impaired barrier function, epithelial remodelling, and increased release of inflammatory mediators. In severe asthma, the epithelial barrier repair process is inhibited and the response to insults is exaggerated, driving downstream inflammation. Genetic and epigenetic mechanisms also maintain dysregulation of the epithelial barrier, adding to disease chronicity. Here, we review the role of the airway epithelium in severe asthma and how targeting the epithelium can contribute to asthma treatment.