Collectively, these findings indicate that FoxO1-IRF4 signaling in alveolar macrophages contributes to the type 2 immune response that results in allergic asthmatic inflammation and that pharmacologic inhibition of FoxO1 could be developed as a novel therapeutic approach for treating refractory asthma through regulation of TH2-mediated airway inflammation. The gene discussed is FOXO1; the disease is asthma.