Bronchoconstriction damages airway epithelia by crowding-induced excess cell extrusion

Jody Rosenblatt*, Dustin Bagley, Tobias Russell, Elena Ortiz-Zapater, Sally Stinson, Kristina Fox, Paulina Redd, Merry Joseph, Cassandra Deering-Rice, Christopher Reilly, Maddy Parsons, Christopher Brightling

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Asthma is deemed an inflammatory disease, yet the defining diagnostic feature is mechanical bronchoconstriction. We previously discovered a conserved process called cell extrusion that drives homeostatic epithelial cell death when cells become too crowded. In this work, we show that the pathological crowding of a bronchoconstrictive attack causes so much epithelial cell extrusion that it damages the airways, resulting in inflammation and mucus secretion in both mice and humans. Although relaxing the airways with the rescue treatment albuterol did not affect these responses, inhibiting live cell extrusion signaling during bronchoconstriction prevented all these features. Our findings show that bronchoconstriction causes epithelial damage and inflammation by excess crowding-induced cell extrusion and suggest that blocking epithelial extrusion, instead of the ensuing downstream inflammation, could prevent the feed-forward asthma inflammatory cycle.
Original languageEnglish
Article number6691
Pages (from-to)66-73
Number of pages8
JournalScience
Volume384
Issue number6691
DOIs
Publication statusPublished - 5 Apr 2024

Keywords

  • asthma
  • extrusion
  • epithelial
  • bronchconstriction
  • wound

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