Stat6 is required for mediating responses to IL-4 and for the development of Th2 cells

Interleukin-4 (IL-4) stimulation of cells leads to the activation of multiple signaling pathways, one of which involves State. We have generated State-deficient mice by gene targeting in embryonic stem cells to determine the role of this transcription factor in mediating the biologic functions of IL-4. IL-4-induced increases in the cell surface expression of both MHC class II antigens and IL-4 receptor are completely abrogated, and lymphocytes from State-deficient animals fail to proliferate in response to IL-4. Stat6-deficient B cells do not produce IgE following in vivo immunization with anti-IgD. In addition, State-deficient T lymphocytes fail to differentiate into Th2 cells in response to either IL-4 or IL-13. These results demonstrate that, despite the existence of multiple signaling pathways activated by IL-4, State is essential for mediating responses to IL-4 in lymphocytes.