Roles for claudins in alveolar epithelial barrier function

Terminal airspaces of the lung, alveoli, are sites of gas exchange that are sensitive to disrupted fluid balance. The alveolar epithelium is a heterogeneous monolayer of cells interconnected by tight junctions at sites of cell–cell contact. Paracellular permeability depends on claudin (cldn)‐family tight junction proteins. Of over a dozen alveolar cldns, cldn‐3, cldn‐4, and cldn‐18 are the most highly expressed; other prominent alveolar claudins include cldn‐5 and cldn‐7. Cldn‐3 is primarily expressed by type II alveolar epithelial cells, whereas cldn‐4 and cldn‐18 are expressed throughout the alveolar epithelium. Lung diseases associated with pulmonary edema, such as alcoholic lung syndrome and acute lung injury, affect alveolar claudin expression, which is frequently associated with impaired fluid clearance due to increased alveolar leak. However, recent studies have identified a role for increased cldn‐4 in protecting alveolar barrier function following injury. Thus, alveolar claudins are dynamically regulated, tailoring lung barrier function to control the air–liquid interface.