SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION FACTOR 6 (STAT6)-DEFICIENT MICE ARE PROTECTED FROM ANTIGEN-INDUCED AIRWAY HYPERRESPONSIVENESS AND MUCUS PRODUCTION

The pleiotropic cytokine interleukin 4 (IL-4) has been shown to though t to be important in the allergic diathesis. To determine the mechanis m(s) by which IL-4 mediates allergic airway responses to inhaled aller gens, we compared the effects of antigen sensitization and challenge o n the development of allergic airway responses in mice in which the ne for the signal transducer and activator of transcription factor 6 (St at6) was disrupted to those of their wild-type littermates. Strikingly , Stat6-deficient mice failed to develop airway hyperresponsiveness (A HR), which was observed in their wild-type littermates after allergen provocation. Moreover, antigen-induced increases in mucus-containing c ells were found to be completely Stat6 dependent. Consistent with the lack of Th2 cytokine responses in Stat6-deficient mice, no ovalbumin-s pecific immunoglobulin (Ig)E was detected in their serum. In contrast, Stat6 signaling only partially mediated antigen-induced eosinophilia with no role in vascular adhesion molecule 1 expression. These results indicate that Stat6 signal transduction is critical in the developmen t of allergen-induced AHR and that agents that specifically inhibit th is pathway may provide a novel strategy for the treatment of allergic disorders.