Although glucocorticoids (GCs) are a mainstay in the clinical management of 
asthma, the target cells that mediate their therapeutic effects are unknown. 
Contrary to our expectation, we found that GC receptor (GR) expression in immune 
cells was dispensable for successful therapy of allergic airway inflammation 
(AAI) with dexamethasone. Instead, GC treatment was compromised in mice 
expressing a defective GR in the nonhematopoietic compartment or selectively 
lacking the GR in airway epithelial cells. Further, we found that an intact GR 
dimerization interface was a prerequisite for the suppression of AAI and airway 
hyperresponsiveness by GCs. Our observation that the ability of dexamethasone to 
modulate gene expression in airway epithelial cells coincided with its potency 
to resolve AAI supports a crucial role for transcriptional regulation by the GR 
in this cell type. Taken together, we identified an unknown mode of GC action in 
the treatment of allergic asthma that might help to develop more specific 
therapies in the future.