Bronchoconstriction damages airway epithelia by crowding-induced excess cell extrusion

• DOI: 10.1126/science.adk2758
• Publication Date: 2024-04-04T17:58:54Z
• Authors: Dustin C. Bagley; Tobias Russell; Elena Ortiz-Zapater; Sally Stinson; Kristina Fox; Polly F. Redd; Merry Joseph; Cassandra Deering...; Christopher Reilly; Maddy Parsons; Christopher Brigh...; Jody Rosenblatt
• Keywords: Mechanotransduction

Asthma is deemed an inflammatory disease, yet the defining diagnostic feature mechanical bronchoconstriction. We previously discovered a conserved process called cell extrusion that drives homeostatic epithelial death when cells become too crowded. In this work, we show pathological crowding of bronchoconstrictive attack causes so much it damages airways, resulting in inflammation and mucus secretion both mice humans. Although relaxing airways with rescue treatment albuterol did not affect these responses, inhibiting live signaling during bronchoconstriction prevented all features. Our findings damage by excess crowding-induced suggest blocking extrusion, instead ensuing downstream inflammation, could prevent feed-forward asthma cycle.