Claudin 5 in a murine model of allergic asthma: Its implication and response to steroid treatment

To the Editor: Allergic inflammation develops in tissues with large epithelial surface areas exposed to the environment, such as the lung, skin, and gut.1 In the lung allergens can activate cells in the epithelium to produce cytokines that induce TH2 responses.2 In addition, allergens (eg, the house dust mite Dermatophagoides pteronyssinus proteinase Der p 1) can disrupt epithelial cell tight junctions (TJs), suggesting a role for epithelial barrier function in allergic sensitization and asthma.2 However, less is known about endothelial barrier function in asthmatic patients.3 Increased angiogenesis, vasodilatation, vascular congestion, and edema contribute to thickening of the airway wall and reduction of the airway lumen in asthmatic patients.3 Endothelial cell-cell junctions communicate cell position, limit growth and apoptosis, and regulate vascular homeostasis.3 A component of endothelial TJs, claudins are tetra-membrane-spanning proteins oriented with amino- and carboxy-termini in the cytosol, resulting in the formation of 2 extracellular loops that control TJ adhesion.4 In airway endothelial cells claudin 5 (CLDN5) plays a critical role in controlling endothelial cell polarity and pericellular permeability.4 Previously, altered lung CLDN5 expression was found to be associated with increased susceptibility to acute lung injury in mice.5 In spite of the important role of claudins as regulators of TJ complexes and cell permeability, the role of CLDN5 in the increased vascular permeability seen in asthmatic patients remains poorly characterized. Dexamethasone inhibited the IL-4-induced CLDN5 level increase and restored TEER levels. [...]in the airways increased CLDN5 levels are associated with decreased TEER levels, probably through disruption of pulmonary endothelial cell TJs, which is in accordance with the pulmonary epithelial cell responses noted previously.4 Endothelial cells function as gatekeepers, controlling the infiltration of blood proteins and cells into the vessel wall.