Essential role of Stat6 in IL-4 signalling

Nature. 1996 Apr 18;380(6575):627-30. doi: 10.1038/380627a0.


Interleukin-4 (IL-4) is a pleiotropic lymphokine which plays an important role in the immune system. IL-4 activates two distinct signalling pathways through tyrosine phosphorylation of Stat6, a signal transducer and activator of transcription, and of a 170K protein called 4PS. To investigate the functional role of Stat6 in IL-4 signalling, we generated mice deficient in Stat6 by gene targeting. We report here that in the mutant mice, expression of CD23 and major histocompatibility complex (MHC) class II in resting B cells was not enhanced in response to IL-4. IL-4 induced B-cell proliferation costimulated by anti-IgM antibody was abolished. The T-cell proliferative response was also notably reduced. Furthermore, production of Th2 cytokines from T cells as well as IgE and IgG1 responses after nematode infection were profoundly reduced. These findings agreed with those obtained in IL-4 deficient mice or using antibodies to IL-4 and the IL-4 receptor. We conclude that Stat6 plays a central role in exerting IL-4 mediated biological responses.

MeSH terms

  • Animals
  • Antibodies, Helminth / biosynthesis
  • Antibodies, Helminth / immunology
  • B-Lymphocytes / immunology
  • Cell Line
  • Cells, Cultured
  • Cytokines / biosynthesis
  • Gene Targeting
  • Histocompatibility Antigens Class II / biosynthesis
  • Immunoglobulin A / biosynthesis
  • Immunoglobulin Class Switching / immunology
  • Immunoglobulin E / biosynthesis
  • Immunoglobulin G / biosynthesis
  • Interleukin-4 / metabolism*
  • Lymphocyte Activation / immunology
  • Mice
  • Nippostrongylus / immunology
  • Receptors, IgE / biosynthesis
  • STAT6 Transcription Factor
  • Signal Transduction / physiology*
  • Spleen / cytology
  • T-Lymphocytes / immunology
  • T-Lymphocytes, Helper-Inducer / immunology
  • Trans-Activators / genetics
  • Trans-Activators / physiology*


  • Antibodies, Helminth
  • Cytokines
  • Histocompatibility Antigens Class II
  • Immunoglobulin A
  • Immunoglobulin G
  • Receptors, IgE
  • STAT6 Transcription Factor
  • Stat6 protein, mouse
  • Trans-Activators
  • Interleukin-4
  • Immunoglobulin E