Impaired IL-12 responses and enhanced development of Th2 cells in Stat4- deficient mice

Mark Kaplan, Y. L. Sun, T. Hoey, M. J. Grusby

Research output: Contribution to journalArticle

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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) proteins. Stat4 is one member of this family, 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.

Original languageEnglish (US)
Pages (from-to)174-177
Number of pages4
JournalNature
Volume382
Issue number6587
DOIs
StatePublished - 1996
Externally publishedYes

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Th2 Cells
Interleukin-12
Th1 Cells
Lymphocytes
STAT Transcription Factors
Cytokine Receptors
Gene Targeting
Listeria monocytogenes
Natural Killer Cells
Interferons
Transcription Factors
Cell Proliferation
Cytokines

ASJC Scopus subject areas

  • General

Cite this

Impaired IL-12 responses and enhanced development of Th2 cells in Stat4- deficient mice. / Kaplan, Mark; Sun, Y. L.; Hoey, T.; Grusby, M. J.

In: Nature, Vol. 382, No. 6587, 1996, p. 174-177.

Research output: Contribution to journalArticle

Kaplan, Mark ; Sun, Y. L. ; Hoey, T. ; Grusby, M. J. / Impaired IL-12 responses and enhanced development of Th2 cells in Stat4- deficient mice. In: Nature. 1996 ; Vol. 382, No. 6587. pp. 174-177.
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