Figure 1.

Schematic model for airway surface liquid (ASL) thickness regulation (modified from References [22,96]). In airway epithelial cells, interleukin (IL)-4 and IL-13 increase Cl⁻ secretion acting on expression and/or activity of cystic fibrosis transmembrane conductance regulator (CFTR) and calcium-activated chloride channels (CaCCs) while decreasing Na⁺ reabsorption through epithelium sodium channels (EnaCs). This would result in a higher ion concentration in the lumen, with water following the osmotic gradient and increasing ASL thickness. IL-4 and IL-13, however, increase pendrin expression, thus leading to Cl⁻ reabsorption and HCO₃⁻ secretion. HCO₃⁻ is then combined with H⁺ and transformed to CO₂ and H₂O by the carbonic anhydrase (CA) enzymes in the lumen, leading to net water reabsorption and eventually decreasing ASL thickness.