Signal transducer and activator of transcription 6 controls chemokine production and T helper cell type 2 cell trafficking in allergic pulmonary inflammation

Antigen-specific CD4 T helper type 2 (Th2) cells play a pivotal role in the induction of allergic asthma, but the mechanisms regulating their recruitm ent into the airways are unknown. Signal transducer and activator of transc ription factor (Stat)6 is a transcription factor essential for Th2 cell dif ferentiation. Here we show that Stat6 also controls Th2 cell recruitment an d effector function in allergic inflammation in vivo. To isolate the role o f Stat6 in regulating Th2 cell trafficking and effector function from its r ole in Th2 cell differentiation, we used a murine model of asthma in which in vitro-differentiated Stat6(+/+) antigen-specific Th2 cells were adoptive ly transferred into naive Stat6(-/-) and Stat6(+/+) mice followed by aeroso l antigen challenge. We found that all of the features of asthma, including Th2 cell accumulation, Th2 and eosinophil-active chemokine production, and airway eosinophilia, mucus production, and hyperresponsiveness seen in Sta t6(+/+) mice, were dramatically absent in Stat6(-/-) mice that received Sta t6(+/+) antigen-specific Th2 cells. Our findings establish Stat6 as essenti al for the Th2 cell trafficking and effector function and suggest that inte rruption of Stat6 signaling in resident cells of the lung is a novel approa ch to asthma therapy.