Stat4 regulates multiple components of IFN-γ-inducing signaling pathways

V. A. Lawless, S. Zhang, O. N. Ozes, H. A. Bruns, I. Oldham, T. Hoey, M. J. Grusby, M. H. Kaplan

Research output: Contribution to journalArticle

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Abstract

Stat4 is activated in response to IL-12. Most functions of IL-12, including the induction of IFN-γ, are compromised in the absence of Stat4. Since the precise role of Stat4 in IFN-γ induction has not been established, experiments were conducted to examine Stat4 activation of IFN-γ and other genes required for cytokine-induced expression of IFN-γ. We first examined IL-12 signaling components. Basal expression of IL-12Rβ1 and IL-12Rβ2 is decreased in Stat4-deficient cells compared with that in control cells. However, IL-12 was still capable of inducing equivalent phosphorylation of Jak2 and Tyk2 in wild-type and Stat4-deficient activated T cells. We have further determined flint other cytokine signaling pathways that induce IFN-γ production are defective in the absence of Stat4. IL-18 induces minimal IFN-γ production from Stat4-deficient activated T cells compared with control cells. This is due to defective IL-18 signaling, which results from the lack of IL-12-induced, and Stat4-dependent, expression of the IL-18R. Following IL-12 pretreatment to induce IL-18R, wild-type, but not Stat4-deficient, activated T cells demonstrated IL-18-induced NF-κB DNA-binding activity. In addition, IL-12-pretreated Stat4-deficient activated T cells have minimal IFN-γ production followed by stimulation with IL-18 alone or in combination with IL-12 compared with control cells. Thus, Stat4 activation by IL-12 is required for the function of multiple cytokine pathways that result in induction of IFN-γ.

Original languageEnglish (US)
Pages (from-to)6803-6808
Number of pages6
JournalJournal of Immunology
Volume165
Issue number12
StatePublished - Dec 15 2000

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Interleukin-12
Interleukin-18
T-Lymphocytes
Cytokines
Phosphorylation
DNA

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Lawless, V. A., Zhang, S., Ozes, O. N., Bruns, H. A., Oldham, I., Hoey, T., ... Kaplan, M. H. (2000). Stat4 regulates multiple components of IFN-γ-inducing signaling pathways. Journal of Immunology, 165(12), 6803-6808.

Stat4 regulates multiple components of IFN-γ-inducing signaling pathways. / Lawless, V. A.; Zhang, S.; Ozes, O. N.; Bruns, H. A.; Oldham, I.; Hoey, T.; Grusby, M. J.; Kaplan, M. H.

In: Journal of Immunology, Vol. 165, No. 12, 15.12.2000, p. 6803-6808.

Research output: Contribution to journalArticle

Lawless, VA, Zhang, S, Ozes, ON, Bruns, HA, Oldham, I, Hoey, T, Grusby, MJ & Kaplan, MH 2000, 'Stat4 regulates multiple components of IFN-γ-inducing signaling pathways', Journal of Immunology, vol. 165, no. 12, pp. 6803-6808.
Lawless VA, Zhang S, Ozes ON, Bruns HA, Oldham I, Hoey T et al. Stat4 regulates multiple components of IFN-γ-inducing signaling pathways. Journal of Immunology. 2000 Dec 15;165(12):6803-6808.
Lawless, V. A. ; Zhang, S. ; Ozes, O. N. ; Bruns, H. A. ; Oldham, I. ; Hoey, T. ; Grusby, M. J. ; Kaplan, M. H. / Stat4 regulates multiple components of IFN-γ-inducing signaling pathways. In: Journal of Immunology. 2000 ; Vol. 165, No. 12. pp. 6803-6808.
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