Impaired IL-12 responses and enhanced development of Th2 cells in Stat4-deficient mice (original) (raw)

Nature volume 382, pages 174–177 (1996)Cite this article

Abstract

INTERACTIONS between cytokine and receptor lead to the activation of multiple signalling molecules, including the family of signal transducer and activator of transcription (STAT) proteins1,2. Stat4 is one member of this family3,4, and is activated only in response to the cytokine interleukin(IL)-12 (refs 5, 6). By gene targeting, we have generated mice deficient in Stat4 to determine whether the function of this transcription factor is redundant with other signalling molecules activated by IL-12. IL-12-induced increases in the production of interferon(IFN)-γ cellular proliferation and natural killer (NK) cell cytotoxicity are abrogated in lymphocytes from Stat4-deficient mice. The development of Th1 cells in response to either IL-12 or Listeria monocytogenes is also impaired in the absence of Stat4. Furthermore, Stat4-deficient lymphocytes demonstrate a propensity towards the development of Th2 cells. These results demonstrate that Stat4 is essential for mediating responses to IL-12 in lymphocytes, and regulating the differentiation of both Th1 and Th2 cells.

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Authors and Affiliations

  1. Department of Cancer Biology, Harvard School of Public Health, Boston, Massachusetts, 02115, USA
    Mark H. Kaplan & Michael J. Grusby
  2. Tularik, Inc., 270 East Grand Avenue, South San Francisco, California, 94080, USA
    Ya-Lin Sun & Timothy Hoey
  3. Department of Medicine, Harvard Medical School, Boston, Massachusetts, 02115, USA
    Michael J. Grusby

Authors

  1. Mark H. Kaplan
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  2. Ya-Lin Sun
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  3. Timothy Hoey
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  4. Michael J. Grusby
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Kaplan, M., Sun, YL., Hoey, T. et al. Impaired IL-12 responses and enhanced development of Th2 cells in Stat4-deficient mice.Nature 382, 174–177 (1996). https://doi.org/10.1038/382174a0

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