Role of STAT6 in IgE receptor/FcεRI-mediated late phase allergic responses of mast cells

In this study we show that IgE receptor engagement triggers activation of STAT6 in mast cells. We sought to determine the role of STAT6 activation in IgE receptor-mediated mast cell responses using STAT6 knockout mice. After IgE receptor engagement, bone marrow mast cells from STAT6^-/- mice exhibited normal histamine and leukotriene C₄ release, but their cytokine release was markedly reduced. In accordance with these in vitro data, IgE/Ag-challenged STAT6^-/- mice showed normal early phase, but severely impaired late phase, allergic reactions. These findings provide unprecedented evidence that STAT6 plays a pivotal role in mast cell responses to IgE/Ag stimulation.