Year: 2023
Type: preprint
Abstract: Asthma is deemed an inflammatory disease, yet the defining diagnostic symptom is mechanical bronchoconstriction. We previously discovered a conserved process that drives homeostatic epithelial cell death in response to mechanical cell crowding called cell extrusion(1, 2). Here, 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. While relaxing airways with the rescue treatment albuterol did not impact these responses, inhibiting live cell extrusion signaling during bronchoconstriction prevented all these symptoms. Our findings propose a new etiology for asthma, dependent on the mechanical crowding of a bronchoconstrictive attack. Our studies suggest that blocking epithelial extrusion, instead of ensuing downstream inflammation, could prevent the feed-forward asthma inflammatory cycle.
Authors: Dustin C. Bagley, Tobias Russell, Elena Ortiz-Zapater, Kristina Fox, Polly F. Redd, Merry Joseph, Cassandra Deering-Rice, Christopher Reilly, Maddy Parsons, Jody Rosenblatt
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: University of Utah, American Asthma Foundation, Queen Mary University of London, Huntsman Cancer Institute, University of Southampton, Imperial College London, King's College London, University College London, Biotechnology and Biological Sciences Research Council, National Center for Research Resources
OpenAlex ID: W4385568941