The role of epithelial cell extrusion in asthma

Asthma is an airway inflammatory disease, defined by bronchoconstrictive attacks that can be life-threatening. The two essential tissue components of the bronchioles are the airway epithelium and the underlying smooth muscle. In asthma, the smooth muscle is remodelled and becomes hyper-responsive, leading to excessive contractility. We have shown that epithelia are exquisitely sensitive to mechanical forces. Cell crowding triggers cell extrusion, while stretching triggers cell division. We recently discovered that the asthmatic bronchoconstrictive attack, causes excess airway epithelial extrusion and damage, compromising the barrier function, leading to inflammation. We propose that in healthy lungs, epithelia and smooth muscle communicate with each other to ensure sufficient epithelial cells numbers, essential to a tight barrier. However, in asthma, excess epithelial extrusion signals smooth muscle remodeling, actuating further rounds of more intense bronchoconstriction. This feed-forward cycle could perpetuate asthma attacks. We believe that our mechanochemical and cell biological insight into asthma will reveal novel ways to prevent it. We will investigate this hypothesis by addressing the following questions: 1) How are airways remodelled to cause an attack? 2) Do epithelia regulate constriction? 3) Does extrusion shed rhinovirus, yet trigger asthma attack