Epithelial-Neural Interactions Dynamically Protect the Airway

Abstract

Every breath exposes our airways to potential threats - chemicals, gastric acid, food, or liquids - which can damage the respiratory epithelium, induce inflammation, and acutely impair breathing. Our airways have multiple sensory systems that detect these threats to trigger protective reflexes like coughing and swallowing. We found that rare epithelial cells in the trachea and larynx called neuroendocrine (NE) cells are sensitive to commonly aspirated noxious stimuli, water and acid, and upon stimulation release ATP to activate purinoreceptivesensory nerve fibers to initiate swallowing and cough-like reflexes. This work uncovered striking molecular and biophysical diversity of NE cells across the airways and revealed mechanisms by which these specialized cells serve as sentinels for activating airway protective circuits. We are now investigating whether other molecularly distinct sensory epithelial cell types contribute to airway protection, how their properties change in human airway disease, and whether dysregulation of these cells underlies disorders of airway hyper- or hyposensitivity.