The role of epithelial cell extrusion in asthma

Asthma is an airway inflammatory disease. Sheets of cells line these airways create a barrier that prevents pathogens and toxins from getting inside. Maintaining the proper numbers of cells is critical. We have shown that mechanical forces regulates cell numbers. Too many cells leads to crowding, causing cells to extrude out of the sheet and die. Too few cells leads to cell stretching, causing the number of cells to increase by division so no gaps form. During an asthma attack musculature constricts airways and causes excess cell crowding and extrusion, leaving gaps in the barrier that cause inflammation and infection. We propose that the compromised barrier leads to further constriction and multiple cycles of asthma attacks. Our approach to asthma focuses on the mechanics controlling cells comprising the barrier and their influence on the muscle cells that control constriction. This novel insight could lead to therapies that prevent asthma attacks.