Stat6 is required for mediating responses to IL-4 and for development of Th2 cells.
Interleukin-4 (IL-4) stimulation of cells leads to the activation of multiple signaling pathways, one of which involves Stat6. We have generated Stat6-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 Stat6-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, Stat6-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, Stat6 is essential for mediating responses to IL-4 lymphocytes.
Kaplan
M H
MH
Department of Cancer Biology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Schindler
U
U
Smiley
S T
ST
Grusby
M J
MJ
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D007073:Immunoglobulin E / Q000096:biosynthesis; D015847:Interleukin-4 / Q000276:immunology / Q000502:physiology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics; D008565:Membrane Proteins / Q000096:biosynthesis; D051379:Mice; D008817:Mice, Mutant Strains; D050800:STAT6 Transcription Factor; D015398:Signal Transduction / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects; D018418:Th2 Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D015854:Up-Regulation / Q000276:immunology
D008565:Membrane Proteins; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D015847:Interleukin-4; D007073:Immunoglobulin E