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FOXP3 — IL2
Pathways - manually collected, often from reviews:
Protein-Protein interactions - manually collected from original source literature:
Studies that report less than 10 interactions are marked with *
Text-mined interactions from Literome
Allan et al., J Clin Invest 2005
:
Surprisingly, although ectopic expression of
FOXP3 in human CD4+ T cells
resulted in induction of hyporesponsiveness and suppression of
IL-2 production, it did not lead to acquisition of significant suppressor activity in vitro
Kashiwada et al., J Immunol 2006
(Splenomegaly) :
Interestingly, the CD4 ( + ) T cells from SHIP KO and Dok-1/SHIP DKO mice produced higher levels of TGF-beta, expressed
Foxp3 , and
inhibited IL-2 production by CD3 stimulated CD4 ( + ) CD25 ( - ) T cells in vitro
Zorn et al., Blood 2006
(Leukemia, Myelogenous, Chronic, BCR-ABL Positive...) :
IL-2 regulates
FOXP3 expression in human CD4+CD25+ regulatory T cells through a STAT dependent mechanism and induces the expansion of these cells in vivo ... In vitro,
IL-2 selectively
up-regulated the expression of
FOXP3 in purified CD4+CD25+ T cells but not in CD4+CD25- cells
Chen et al., J Biol Chem 2006
:
Ectopic expression of
Foxp3 in non-T ( reg )
leads to repression of the
interleukin 2 (IL-2) and interferon gamma (IFNgamma) genes, gain of suppressor function, and induction of genes such as CD25, GITR, and CTLA-4, but the mode by which Foxp3 enforces this program is unclear
Murawski et al., Ann N Y Acad Sci 2006
(Diabetes Mellitus) :
Upregulation of
Foxp3 expression in mouse and human Treg is
IL-2/STAT5 dependent : implications for the NOD STAT5B mutation in diabetes pathogenesis
Carrier et al., J Immunol 2007
(Autoimmune Diseases) :
We found that the induction, differentiation, and function of TGF-beta derived
Foxp3 ( + ) Th3 cells were
independent of
IL-2 , which differs from thymic Tregs ... Accumulation of
Foxp3 ( + ) cells over time, however, was
dependent on
IL-2
Gavin et al., Nature 2007
:
It has been suggested that
Foxp3 expression is
required for both survival of Tr precursors as well as their inability to produce
interleukin (IL)-2 and independently proliferate after T-cell-receptor engagement, raising the possibility that such ` anergy ' and Tr suppressive capacity are intimately linked
Zheng et al., J Immunol 2007
(Autoimmune Diseases) :
Although others have reported that
IL-2 can directly
enhance forkhead box protein P3 (Foxp3) transcription factor expression by natural CD4 ( + ) CD25 ( + ) regulatory T cells, in this study, we report that the role of IL-2 on the generation of peripheral regulatory CD4 ( + ) cells is indirect ... Ab neutralization studies and experiments with IL-2-deficient mice have revealed that
IL-2 is
required for TGF-beta to induce naive CD4 ( + ) CD25 ( - ) cells to become CD25 ( + ) and express
Foxp3 , and develop the characteristic properties of CD4 ( + ) CD25 ( + ) regulatory cells ... This
effect of
IL-2 on the generation and expansion of these adaptive
Foxp3 ( + ) regulatory cells is nonredundant, but IL-4, IL-7, and IL-15, other common gamma-chain cytokines, could sustain Foxp3 expression
Li et al., Proc Natl Acad Sci U S A 2007
:
A minimum
FOXP3 ensemble containing native TIP60 and HDAC7 is
necessary for
IL-2 production regulation in T cells
Davidson et al., J Immunol 2007
:
IL-2 plays a non-redundant role in TGF-beta induced
Foxp3 expression
Ahmadzadeh et al., J Immunother 2007
(Melanoma...) :
IL-2 and IL-15 each
mediate de novo induction of
FOXP3 expression in human tumor antigen-specific CD8 T cells ... Here, we demonstrate that
interleukin-2 (IL-2) induces
FOXP3 expression in OKT3 stimulated or antigen stimulated CD8 T cells, indicating that FOXP3 expression is neither limited to a unique subset of CD8 T cells nor dependent on the mode of T-cell receptor stimulation
Holmes et al., J Biol Chem 2007
:
FoxP3 determines the development of CD4+CD25+ regulatory T ( Treg ) cells and
represses interleukin-2 (IL-2) expression in Treg cells
Souto-Carneiro et al., Immunol Lett 2007
:
Investigation of the mode of action of regulatory T cells indicated that
FOXP3 binds the heterodimeric transcription factor AML1 and
suppresses AML1 enhanced
IL-2 production
Passerini et al., Int Immunol 2008
:
Expression of
FOXP3 in activated Teff cells
requires both TCR mediated activation and endogenous
IL-2 , but is not dependent on cell division and does not induce suppressive function
Lan et al., J Autoimmun 2008
:
In regulatory T cells,
IL-2 signaling
upregulates the expression of
FoxP3
Wuest et al., J Leukoc Biol 2008
:
Binding of
IL-2 to its receptor leads to phosphorylation of STAT5, and binding of phosphorylated STAT5 to the foxp3 promoter
increases foxp3 transcription, resulting in elevated levels of
FoxP3 protein in Tregs
Smith et al., Immunol Rev 2008
:
In contrast, we found no evidence that
FOXP3 ( + ) cells actively
suppress IL-2 expression, thereby failing to support the notion that such cells regulate potential effector cells
Chaput et al., Gut 2009
(Adenocarcinoma...) :
Finally,
interleukin 6 and TGF beta 1 synergistically
induced the generation of CD8 ( + ) CD25 ( + )
Foxp3 ( + ) T cells ex vivo
Kitamura et al., Int J Cancer 2009
(Neoplasms) :
Foxp3 expression on Tregs was
reduced by OX40 costimulation, but not by
IL-2 stimulation
Yarkoni et al., Eur J Immunol 2009
(Body Weight...) :
Similar effects of the fusion proteins were observed in healthy mice :
IL2-DT caused lymphopenia and IL2-cas
increased fractional expression of
FoxP3
Milkova et al., Exp Dermatol 2010
:
The NF-kappaB signalling pathway is involved in the
LPS/IL-2 induced upregulation of
FoxP3 expression in human CD4+CD25high regulatory T cells
Long et al., Diabetes 2010
(Diabetes Mellitus, Type 1) :
The
effects of
IL-2 on
FOXP3 induction were assessed 48 h after activation of CD4 ( + ) CD25 ( - ) T-cells with anti-CD3 antibody
Lucchi et al., Interactive cardiovascular and thoracic surgery 2010
(Mesothelioma...) :
Tryptase MCs, CD8+ and
Foxp3+ lymphocytes had significantly
increased in the
interleukin 2 (IL-2) treated group
Sgouroudis et al., Autoimmunity 2011
:
IL-2 production by dendritic cells
promotes Foxp3 ( + ) regulatory T-cell expansion in autoimmune-resistant NOD congenic mice
Goudy et al., Eur J Immunol 2011
(Diabetes Mellitus, Type 1) :
Increasing levels of
IL-2 in vivo also
resulted in larger numbers of CD62L ( hi )
FoxP3 ( + ) Tregs in NOD mice ... In NOD mice, reduced
IL-2 expression
leads to an increase in nonsuppressive CD62L ( lo )
FoxP3 ( + ) Tregs, which in turn correlates with a pool of CD62L ( hi ) FoxP3 ( + ) Tregs with limited proliferation
Chen et al., J Immunol 2011
:
IL-2 controls the stability of
Foxp3 expression in TGF-beta induced Foxp3+ T cells in vivo
D'Alise et al., Proc Natl Acad Sci U S A 2011
(Diabetes Mellitus...) :
Foxp3 ( + ) regulatory T cells ( Tregs ) originate in the thymus, but the Treg phenotype can also be
induced in peripheral lymphoid organs or in vitro by stimulation of conventional CD4 ( + ) T cells with
IL-2 and TGF-ß
Grigoriadis et al., PloS one 2011
:
While the subsequent
IL-2 induction of
Foxp3 in nTreg precursors requires c-Rel, this developmental transition does not coincide with the nuclear expression of c-Rel ... Collectively, our results support a model of nTreg differentiation in which c-Rel generates a permissive state for foxp3 transcription during the development of nTreg precursors that influences the subsequent
IL-2 dependent
induction of
Foxp3 without a need for c-Rel reactivation
Chen et al., J Immunol 2012
(Tuberculosis, Pulmonary) :
IL-2 treatments early after Mycobacterium tuberculosis infection of macaques
induced simultaneous expansion of CD4 ( + ) CD25 ( + ) Foxp3 ( + ) Treg, CD8 ( + ) CD25 ( + )
Foxp3 ( + ) T cells, and CD4 ( + ) T effector/CD8 ( + ) T effector/V?2Vd2 T effector populations producing anti-M
Polhill et al., J Am Soc Nephrol 2012
(Glomerulosclerosis, Focal Segmental...) :
IL-2/IL-2Ab reduced serum IL-6 and renal expression of IL-6 and IL-17 but
enhanced expression of IL-10 and
Foxp3 in the spleen
Shameli et al., Eur J Immunol 2013
(Diabetes Mellitus, Type 1) :
IL-2 plays a critical role in both effector T-cell development and
FoxP3 ( + ) CD4 ( + ) Treg-cell homeostasis
Wang et al., Transplant Proc 2013
:
We explored the
effect of rapamycin ( RAPA ) and
interleukin (IL)-2 on regulatory CD4 ( + ) CD25 ( + )
Foxp3 ( + ) T cells ( Treg ) in recipient mice after allogenic corneal transplantation and analyzed its correlation with graft outcome
Guo et al., J Immunol 2013
(Colitis) :
Thus,
IL-2/Stat5 signaling may be
critical for
Foxp3 induction in peripheral CD4 ( + ) CD25 ( + ) Foxp3 ( - ) iTreg precursors ... In this study, to further define the
role of
IL-2 in the formation of iTreg precursors as well as their subsequent
Foxp3 expression, we designed a two-step iTreg differentiation model ... In consideration of this information, whereas initial inhibition of IL-2 signaling upon T cell priming generates iTreg precursors, subsequent activation of
IL-2 signaling in these precursors
induces the expression of
Foxp3