Polarity in respiratory development, homeostasis and disease

The respiratory system is composed of a multitude of cells that organize to form complex branched airways that end in alveoli, which respectively function to guide air flow and mediate gas exchange with the bloodstream. The organization of the respiratory sytem relies on distinct forms of cell polarity, which guide lung morphogenesis and patterning in development and provide homeostatic barrier protection from microbes and toxins. The stability of lung alveoli, the luminal secretion of surfactants and mucus in the airways, and the coordinated motion of multiciliated cells that generate proximal fluid flow, are all critical functions regulated by cell polarity, with defects in polarity contributing to respiratory disease etiology. Here, we summarize the current knowledge of cell polarity in lung development and homeostasis, highlighting key roles for polarity in alveolar and airway epithelial function and outlining relationships with microbial infections and diseases, such as cancer.