Frontline

Absence of functional STAT4 activation despite detectable tyrosine phosphorylation induced by murine IFN-α

Lisa S. Berenson, J. David Farrar, Theresa L. Murphy, Kenneth M. Murphy

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

We previously reported that IL-12, but not IFN-αA/D, induces T helper type (Th) 1 development and STAT4 phosphorylation in murine CD4+ T cells. However, a recent study reported that IFN-αA/D and recombinant murine IFN-αA can induce STAT4 phosphorylation, although more weakly than IL-12, largely in CD8+ rather than CD4+ T cells. That report did not examine Th1 development or directly demonstrate induction of IFN-γ by IFN-α. To address these differences, we compared IFN-α A/D, murine IFN-αA, and IL-12 for STAT4 phosphorylation, formation of active nuclear DNA binding complexes, induction of Th1 development, and production of IFN-γ in murine CD4+ T cells. IFN-αA induced detectable STAT4 phosphorylation, although at significantly lower levels than induced by IL-12. Furthermore, in contrast to IL-12, IFN-αA failed to induce Th1 development or the formation of DNA binding complexes or to synergize with IL-18 for induction of IFN-γ production. STAT1-deficient CD4+ T cells showed increased IFN-αA-induced STAT4 phosphorylation but still exhibited significantly lower amounts of cytokine-induced IFN-γ compared to IL-12. In summary, these results suggest that in contrast to IL-12, IFN-αA does not play a functionally significant role in meditating the STAT4-dependent induction of Th1 development or IFN-γ production in CD4+ T cells.

Original languageEnglish (US)
Pages (from-to)2365-2374
Number of pages10
JournalEuropean Journal of Immunology
Volume34
Issue number9
DOIs
StatePublished - Sep 2004

Fingerprint

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

Keywords

  • IFN-α
  • IL-12
  • STAT4
  • Th1

ASJC Scopus subject areas

  • Immunology

Cite this

Frontline : Absence of functional STAT4 activation despite detectable tyrosine phosphorylation induced by murine IFN-α. / Berenson, Lisa S.; Farrar, J. David; Murphy, Theresa L.; Murphy, Kenneth M.

In: European Journal of Immunology, Vol. 34, No. 9, 09.2004, p. 2365-2374.

Research output: Contribution to journalArticle

@article{3f719988295e4592a19c28dd8cd4a38e,
title = "Frontline: Absence of functional STAT4 activation despite detectable tyrosine phosphorylation induced by murine IFN-α",
abstract = "We previously reported that IL-12, but not IFN-αA/D, induces T helper type (Th) 1 development and STAT4 phosphorylation in murine CD4+ T cells. However, a recent study reported that IFN-αA/D and recombinant murine IFN-αA can induce STAT4 phosphorylation, although more weakly than IL-12, largely in CD8+ rather than CD4+ T cells. That report did not examine Th1 development or directly demonstrate induction of IFN-γ by IFN-α. To address these differences, we compared IFN-α A/D, murine IFN-αA, and IL-12 for STAT4 phosphorylation, formation of active nuclear DNA binding complexes, induction of Th1 development, and production of IFN-γ in murine CD4+ T cells. IFN-αA induced detectable STAT4 phosphorylation, although at significantly lower levels than induced by IL-12. Furthermore, in contrast to IL-12, IFN-αA failed to induce Th1 development or the formation of DNA binding complexes or to synergize with IL-18 for induction of IFN-γ production. STAT1-deficient CD4+ T cells showed increased IFN-αA-induced STAT4 phosphorylation but still exhibited significantly lower amounts of cytokine-induced IFN-γ compared to IL-12. In summary, these results suggest that in contrast to IL-12, IFN-αA does not play a functionally significant role in meditating the STAT4-dependent induction of Th1 development or IFN-γ production in CD4+ T cells.",
keywords = "IFN-α, IL-12, STAT4, Th1",
author = "Berenson, {Lisa S.} and Farrar, {J. David} and Murphy, {Theresa L.} and Murphy, {Kenneth M.}",
year = "2004",
month = "9",
doi = "10.1002/eji.200324829",
language = "English (US)",
volume = "34",
pages = "2365--2374",
journal = "European Journal of Immunology",
issn = "0014-2980",
publisher = "Wiley-VCH Verlag",
number = "9",

}

TY - JOUR

T1 - Frontline

T2 - Absence of functional STAT4 activation despite detectable tyrosine phosphorylation induced by murine IFN-α

AU - Berenson, Lisa S.

AU - Farrar, J. David

AU - Murphy, Theresa L.

AU - Murphy, Kenneth M.

PY - 2004/9

Y1 - 2004/9

N2 - We previously reported that IL-12, but not IFN-αA/D, induces T helper type (Th) 1 development and STAT4 phosphorylation in murine CD4+ T cells. However, a recent study reported that IFN-αA/D and recombinant murine IFN-αA can induce STAT4 phosphorylation, although more weakly than IL-12, largely in CD8+ rather than CD4+ T cells. That report did not examine Th1 development or directly demonstrate induction of IFN-γ by IFN-α. To address these differences, we compared IFN-α A/D, murine IFN-αA, and IL-12 for STAT4 phosphorylation, formation of active nuclear DNA binding complexes, induction of Th1 development, and production of IFN-γ in murine CD4+ T cells. IFN-αA induced detectable STAT4 phosphorylation, although at significantly lower levels than induced by IL-12. Furthermore, in contrast to IL-12, IFN-αA failed to induce Th1 development or the formation of DNA binding complexes or to synergize with IL-18 for induction of IFN-γ production. STAT1-deficient CD4+ T cells showed increased IFN-αA-induced STAT4 phosphorylation but still exhibited significantly lower amounts of cytokine-induced IFN-γ compared to IL-12. In summary, these results suggest that in contrast to IL-12, IFN-αA does not play a functionally significant role in meditating the STAT4-dependent induction of Th1 development or IFN-γ production in CD4+ T cells.

AB - We previously reported that IL-12, but not IFN-αA/D, induces T helper type (Th) 1 development and STAT4 phosphorylation in murine CD4+ T cells. However, a recent study reported that IFN-αA/D and recombinant murine IFN-αA can induce STAT4 phosphorylation, although more weakly than IL-12, largely in CD8+ rather than CD4+ T cells. That report did not examine Th1 development or directly demonstrate induction of IFN-γ by IFN-α. To address these differences, we compared IFN-α A/D, murine IFN-αA, and IL-12 for STAT4 phosphorylation, formation of active nuclear DNA binding complexes, induction of Th1 development, and production of IFN-γ in murine CD4+ T cells. IFN-αA induced detectable STAT4 phosphorylation, although at significantly lower levels than induced by IL-12. Furthermore, in contrast to IL-12, IFN-αA failed to induce Th1 development or the formation of DNA binding complexes or to synergize with IL-18 for induction of IFN-γ production. STAT1-deficient CD4+ T cells showed increased IFN-αA-induced STAT4 phosphorylation but still exhibited significantly lower amounts of cytokine-induced IFN-γ compared to IL-12. In summary, these results suggest that in contrast to IL-12, IFN-αA does not play a functionally significant role in meditating the STAT4-dependent induction of Th1 development or IFN-γ production in CD4+ T cells.

KW - IFN-α

KW - IL-12

KW - STAT4

KW - Th1

UR - http://www.scopus.com/inward/record.url?scp=4644368384&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4644368384&partnerID=8YFLogxK

U2 - 10.1002/eji.200324829

DO - 10.1002/eji.200324829

M3 - Article

VL - 34

SP - 2365

EP - 2374

JO - European Journal of Immunology

JF - European Journal of Immunology

SN - 0014-2980

IS - 9

ER -