Identifiers
HUGO:STAT3
Maps_Modules
MACROPHAGE
MDSC
DENDRITIC_CELL
NATURAL_KILLER
NEUTROPHIL
MODULE:INPUT_INHIBITORS
MODULE:IMMUNE_SUPPRESSION
MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS
MODULE:INPUT_ACTIVATORS
MODULE:IMMUNE_STIMULATION
MODULE:IMMUNOSTIMULATORY_CYTOKINE_PATHWAYS
CASCADE:IL10
CASCADE:IL4
CASCADE:IL13
CASCADE:IL6
CASCADE:GSF3
CASCADE:IL15
CASCADE:IL21
CASCADE:FLT3LG
CASCADE:IFNG
CASCADE:IFNAB
References
21115385, PMID:7543512
The binding of IL-10 to its receptor activates JAK1
Two tyrosines (Tyr 446 and Tyr 496) of IL-10RA
are phosphorylated by the JAK1, to which
the transcription factor STAT3 binds via its SH2 domain
and in turn becomes itself phosphorylated.
PMID:10347215
Only JAK1/STAT3 pathway (but not TYK) plays role in
anti-inflammatory action of IL10 in macrophages.
PMID:12223527
Stat proteins 1 alpha, 3, 5A, 5B, and 6 are phosphorylated in response to IL-13.
IL-4, in contrast to IL-13, induced very low levels of phosphorylation of Stats 1 and 5 and a more robust phosphorylation of Stat3 and Stat6.
PMID:23124025
Stat3 activation (tyr 705) by IL-4 requires Jak1 kinase in monocytes
PMID:15218058
Stat3 binds ILR1N promoter and upregulates expression of IL1RN downstream of IL10
PMID:14607900
FNG inhibits IL10 signalind via STAT1.
STAT1 overexpression prevents STAT3 homodimerization.
PMID:23454751
MDSC showed high phosphorylated STAT3 levels that correlated with arginase-I expression levels and activity.
phosphorylated STAT3 binds to multiple sites in the arginase-I promoter. Rescue of arginase-I activity after STAT3 blockade restored MDSC’s suppressive function.
Taken together, these results demonstrate that the suppressive function of arginase-I in both infiltrating and circulating MDSC is a downstream target of activated STAT3.
PMID:20581311
STAT3 as an essential mediator of emergency granulopoiesis by its regulation of transcription factors that direct G-CSF-responsive myeloid progenitor expansion.
STAT3 directly controls G-CSF-dependent expression of CCAAT-enhancer-binding protein β (C/EBPβ), a crucial factor in the emergency granulopoiesis response. Moreover, STAT3 and C/EBPβ coregulate c-Myc through interactions with the c-myc promoter that control the duration of C/EBPα occupancy during demand-driven granulopoiesis.
PMID:19380816
MDSC-induced immune suppression is mediated by reactive oxygen species (ROS).
STAT3 mediates the function of MDSCs by regulating NADPH oxidase (NOX2) expression
In the absence of NOX2 activity, MDSC lost the ability to suppress T cell responses
PMID:20093776
IL6 signaling ilduces STAT3 phosphorylation in MDSC cells.
PMID:20406969
GM-CSF uniquely inhibited signal transducers and activators of transcription (STAT3) and promoted STAT5 activation. STAT5ab(null/null) MDSC were rendered sensitive to sunitinib in the presence of GM-CSF in vitro.
PMID:18776941
Expression of VEGF and bFGF, but also IL-1β, MMP9, CCL2, and CXCL2 is STAT3-dependent in myeloid cells.
PMID:15573129
Constitutively active STAT3 inhibited the functional maturation of DCs in vitro.
PMID:15356132
The activation of STAT3 by IL-6 was required for the suppression of LPS-induced DC maturation. In addition, STAT3 was required for the IL-6-mediated suppression of bone-marrow-derived DC activation and/or maturation.
16286017
IL-6-STAT3 Controls Intracellular MHC Class II αβ Dimer Level through Cathepsin S Activity in Dendritic Cells. IL-6 Stimulation via STAT3 Decreased Cystatin C Expression, Increased the Cathepsin S Activity, and Reduced the MHCII αβ Dimer Level in DCs In Vivo
G-CSF signaling by STAT3 controls c-myc transcription by regulating the ratio of C/EBPα to C/EBPβ at the c-myc promoter
Stat3 activity is required for tumor factor–induced migration of ECs.
PMID:14670306, PMID:16418395
FLT3 sidnaling in Dcs acts via STAT3
PMID:20237412
IFN-β regulates expression of homing and angiogenic factors in neutrophils.
IFNB downregulates expression Cxcr4, Vegf, and Mmp9 in neutrophils
additionally Stat3 and c-myc are downregulated by IFN-β.
(STAT3 is known to be required for full activation of the Cxcr4 gene )
Identifiers
HUGO:STAT3
Maps_Modules
MACROPHAGE
References
PMID:21115385, PMID:7543512
The binding of IL-10 to its receptor activates JAK1
Two tyrosines (Tyr 446 and Tyr 496) of IL-10RA
are phosphorylated by the JAK1, to which
the transcription factor STAT3 binds via its SH2 domain
and in turn becomes itself phosphorylated.
PMID:10347215
Only JAK1/STAT3 pathway (but not TYK) plays role in
anti-inflammatory action of IL10 in macrophages.
→ RECRUITMENT_OF_IMMUNE_CELLS@INNATE_IMMUNE_CELL_Cytosol
→ STAT3@INNATE_IMMUNE_CELL_Cytosol
→ STAT3|pho|active@INNATE_IMMUNE_CELL_Cytosol
→ STAT3|pho|hm2|active@INNATE_IMMUNE_CELL_Cytosol
→ STAT3@INNATE_IMMUNE_CELL_Cytosol
→ STAT3|pho|active@INNATE_IMMUNE_CELL_Cytosol
→ rCST3@INNATE_IMMUNE_CELL_Cytosol
→ rSOCS3@INNATE_IMMUNE_CELL_Cytosol
→ rBCL3@INNATE_IMMUNE_CELL_Cytosol
→ rMAOA@INNATE_IMMUNE_CELL_Cytosol
→ rS100A9@INNATE_IMMUNE_CELL_Cytosol
→ rS100A8@INNATE_IMMUNE_CELL_Cytosol
→ rIL4R@INNATE_IMMUNE_CELL_Cytosol
→ arMIR155@INNATE_IMMUNE_CELL_Cytosol
→ rCXCR4@INNATE_IMMUNE_CELL_Cytosol
→ rCCL2@INNATE_IMMUNE_CELL_Cytosol
→ rCXCL2@INNATE_IMMUNE_CELL_Cytosol
→ rIL1B@INNATE_IMMUNE_CELL_Cytosol
→ rMMP9@INNATE_IMMUNE_CELL_Cytosol
→ rVEGFA@INNATE_IMMUNE_CELL_Cytosol
→ rFGF2@INNATE_IMMUNE_CELL_Cytosol
→ rIL1RN@INNATE_IMMUNE_CELL_Cytosol
→ rIFNG@INNATE_IMMUNE_CELL_Cytosol
→ rIRF8@INNATE_IMMUNE_CELL_Cytosol
→ rPRF1@INNATE_IMMUNE_CELL_Cytosol
→ rMYC@INNATE_IMMUNE_CELL_Cytosol
→ rCEBPB@INNATE_IMMUNE_CELL_Cytosol
→ CEBPB|pho@INNATE_IMMUNE_CELL_Cytosol