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IFNG — STAT4
Pathways - manually collected, often from reviews:
-
NCI Pathway Database IL12 signaling mediated by STAT4:
STAT4 (dimer) complex (STAT4)
→
IFN-gamma (IFNG)
(transcription, activates)
Cai et al., J Immunol 2000*, Schindler et al., J Immunol 2001, Szabo et al., Science 2002, Morinobu et al., Proc Natl Acad Sci U S A 2002, Kobayashi et al., J Exp Med 1989*, Hunter et al., Eur J Immunol 1995*, Kaplan et al., Nature 1996
Evidence: mutant phenotype, assay, other species
-
NCI Pathway Database IL12 signaling mediated by STAT4:
STAT4 (dimer) complex (STAT4)
→
IFN-gamma (IFNG)
(transcription, activates)
Szabo et al., Science 2002, Wittmann et al., J Leukoc Biol 2006
Evidence: mutant phenotype, assay, other species
Text-mined interactions from Literome
Zhang et al., J Immunol 2000
:
We and others have demonstrated that the
Stat4 is
critical for
IFN-gamma production by activated T cells and Th1 cells
Cai et al., J Immunol 2000
(Genetic Predisposition to Disease...) :
However, other signaling pathways can be used to bypass
STAT4 dependent production of
IFN-gamma and enhance innate resistance to T. gondii
Gollob et al., J Immunol 2000
(Immunologic Deficiency Syndromes...) :
These findings demonstrate that the activation of
STAT4 alone is not
sufficient for IL-12 induced
IFN-gamma production and proliferation and suggest that other STATs play a role in these responses to IL-12
Lawless et al., J Immunol 2000
:
Since the precise
role of
Stat4 in
IFN-gamma induction has not been established, experiments were conducted to examine Stat4 activation of IFN-gamma and other genes required for cytokine induced expression of IFN-gamma
Schindler et al., J Immunol 2001
:
The production of
IFN-gamma by IL-12/IL-18 activated macrophages
requires STAT4 signaling and is inhibited by IL-4
Fukao et al., J Immunol 2001
:
The Th2 cytokines IL-4 and IL-10 suppress
Stat4 induction in DC and macrophages when present during maturation and activation, respectively,
diminishing IFN-gamma production
Nakahira et al., J Immunol 2001
:
An absolute requirement for
STAT4 and a
role for
IFN-gamma as an amplifying factor in IL-12 induction of the functional IL-18 receptor complex
Bao et al., J Immunol 2002
(Diabetes Mellitus, Type 1...) :
We then examined whether the change in IL-12 induced
IFN-gamma production by treatment with sex hormones was
due to the regulation of
STAT4 activation
Morinobu et al., Proc Natl Acad Sci U S A 2002
:
We demonstrated that expression of wild-type
STAT4 , but not the S721A mutant,
restored normal T ( H ) 1 differentiation and
IFN-gamma synthesis
Nguyen et al., Science 2002
(Arenaviridae Infections) :
Here we show that IFN-alpha/beta activate
STAT4 directly ( STAT, signal transducers and activators of transcription ) and that this is
required for
IFN-gamma production during viral infections of mice, in concert with T cell receptor derived signals
Nguyen et al., J Immunol 2002
(Herpesviridae Infections) :
IL-12/STAT4 was
critical for NK cell
IFN-gamma expression, whereas IFN-alphabeta/STAT1 were required for induction of cytotoxicity
Hoey et al., EMBO J 2003
:
However,
Stat4alpha is
required for normal levels of IL-12 induced
interferon-gamma production from Th1 cells
Wang et al., J Clin Invest 2003
(Central Nervous System Neoplasms...) :
An immune response also induced in the brain of the GIFN/STAT2-/- mice was associated with
IFN-gamma gene expression by CD3+ T cells and the
activation of the STAT1, STAT3,
STAT4 , and STAT5 molecules
Park et al., Int Immunol 2004
:
A mechanism underlying
STAT4 mediated up-regulation of
IFN-gamma induction inTCR triggered T cells
Mattner et al., J Immunol 2004
(Disease Progression...) :
The IFN-beta induced increase of
IFN-gamma production was
dependent on
STAT4
Berenson et al., Eur J Immunol 2004
:
In summary, these results suggest that in contrast to IL-12, IFN-alphaA does not play a functionally significant role in meditating the
STAT4 dependent induction of Th1 development or
IFN-gamma production in CD4+ T cells
Rodriguez-Galán et al., J Immunol 2005
:
The IL-2-plus-IL-18 or IL-12-plus-IL-18 effect on
IFN-gamma and IL-13 expression is
dependent on
Stat4 and NF-kappaB but independent of Stat6, T-bet, or NFAT
Robertson et al., Blood 2005
(Lymphoma) :
Impaired
interferon-gamma production as a
consequence of
STAT4 deficiency after autologous hematopoietic stem cell transplantation for lymphoma
Suto et al., J Immunol 2005
:
These results indicate that PDCs preferentially produce
IFN-gamma upon IL-4
stimulation by Stat6- and
Stat4 dependent mechanisms
Shin et al., J Immunol 2005
(Asthma) :
STAT4 , which plays a pivotal role in Th1 immune responses,
enhances IFN-gamma transcription in response to the interaction of IL-12 with the IL-12R
Frisancho-Kiss et al., Brain Res 2006
(Coxsackievirus Infections...) :
We have previously reported that IL-12Rbeta1 signaling increases CVB3 induced myocarditis and IL-1beta/IL-18 levels in males, while IL-12 ( p35 )
/STAT4 induced
IFN-gamma does not alter the severity of acute disease
Berenson et al., J Immunol 2006
:
However, in differentiated Th1 cells, IFN-alpha can induce transient, but not sustained,
STAT4 phosphorylation and, in synergy with IL-18, can
induce transient, but not sustained,
IFN-gamma production in Th1 cells, in contrast to the sustained actions of IL-12
Karpuzoglu et al., Endocrinology 2009
:
The activation of STAT4beta was mediated by IL-12 and not IFNgamma because deliberate addition or neutralization of IL-12, but not
IFNgamma ,
affected the activation of
STAT4beta
Kang et al., J Ethnopharmacol 2009
:
STAT4 , but not T-bet, was
involved in the upregulation of
IFN-gamma by SSHT while the increased IL-4 expression was accompanied by a parallel increase in c-Maf but independent of STAT6 and GATA-3
Rottinghaus et al., Immunology 2009
:
Furthermore, we demonstrate that IL-12 induced
STAT-4 activation was
required for T helper type 1 ( Th1 ) cytokine induced
IFN-gamma production in CD8 T cells
Kim et al., Exp Mol Med 2010
(Asthma...) :
Moreover, AHR, non-eosinophilic inflammation, and
IFN-gamma expression were
impaired in allergen challenged IL-12Rbeta2- and
STAT4-deficient mice ; however, AHR and non-eosinophilic inflammation were not impaired in allergen challenged IL-4Ralpha-deficient mice, and these phenomena were accompanied by the enhanced expression of IL-12 and IFN-gamma
Yamamoto et al., Mol Cell Biol 1994
:
Unlike Stat1, neither IFN-alpha nor
IFN-gamma activates
Stat4
Barbulescu et al., J Immunol 1998
:
These data suggest that both AP-1 and
STAT4 are
required for IL-12 dependent
IFN-gamma promoter activity, whereas IL-18 causes direct activation via AP-1
Ahn et al., J Immunol 1998
:
These results indicate that IL-12 has the capacity to induce/maintain STAT4 and STAT5 proteins, and that TYK2 and JAK2 activation correlate with
STAT4 phosphorylation/IFN-gamma induction and STAT5 phosphorylation/cellular proliferation, respectively