Ignet

Gene Information

Gene symbol: STAT6

Gene name: signal transducer and activator of transcription 6, interleukin-4 induced

HGNC ID: 11368

Synonyms: D12S1644, IL-4-STAT

Related Genes

#	Gene Symbol	Number of hits
1	CCND1	1 hits
2	CD1A	1 hits
3	CD1D	1 hits
4	CD8A	1 hits
5	ECD	1 hits
6	GATA3	1 hits
7	IFNG	1 hits
8	IGF1	1 hits
9	IL13	1 hits
10	IL17A	1 hits
11	IL2	1 hits
12	IL4	1 hits
13	IL4R	1 hits
14	IRF3	1 hits
15	ITGAL	1 hits
16	JAK3	1 hits
17	NFKB1	1 hits
18	NUDT6	1 hits
19	SOCS6	1 hits
20	TBK1	1 hits
21	TGFB1	1 hits
22	TLR3	1 hits

Related Sentences

#	PMID	Sentence
1	11101874	We found that interleukin 4 receptor (IL-4R) knockout and downstream signal transducer and activator of transcription 6 (STAT6) knockout, but not IL-4 knockout, mice resisted tumor recurrence, which implicated IL-13, the only other cytokine that uses the IL-4R-STAT6 pathway.
2	12349944	P3CSK4 activates the expression of tumor suppressor protein p53 (p53), c-rel, inhibitor of nuclear factor kappa B (NFkappaB) alpha (IkappaB alpha), type 2 (inducible) nitric oxide (NO) synthase (iNOS), CD40-LR, intercellular adhesion molecule-1 (ICAM-1) and interleukin 1/6/15 (IL-1/6/15).
3	12349944	We detected no activation of heat shock protein (HSP) 27, 60, 84 and 86, osmotic stress protein 94 (Osp 94), IL-12, extracellular signal-regulated protein kinase 1 (ERK1), p38 mitogen activated protein (MAP)-kinase (p38), c-Jun NH2-terminal kinase (JNK), signal transducer and activator of transcription 1 (STAT1), CD14 and caspase genes.
4	12349944	Furthermore, we monitored inhibition of STAT6, Janus kinase 3 (Jak3) and cyclin D1/D3 gene transcription after stimulating bone marrow-derived macrophages (BMDM) with lipopeptide.
5	12441072	Enhanced clearance of herpes simplex virus type 1 and reduced herpetic eye disease in STAT6 knockout mice is associated with increased IL-2.
6	12441072	STAT6 (signal transducers and activators of transcription 6)-deficient (STAT6-/-) mice have defects in IL-4- and IL-13-mediated functions and thus have a reduced T(H)2-mediated immune response.
7	12441072	Lymphocytes from both vaccinated and mock-vaccinated STAT6-/- mice secreted higher amounts of IL-2 than lymphocytes from BALB/c mice, in the presence or absence of stimulation with UV-inactivated HSV-1.
8	12441072	Finally, depletion of IL-2 increased ocular virus replication in STAT6-/- mice to levels similar to that measured in BALB/c mice.
9	12441072	Our results suggest that in the absence of the STAT6 pathway, IL-2-mediated immune responses are up-regulated.
10	12441072	Enhanced clearance of herpes simplex virus type 1 and reduced herpetic eye disease in STAT6 knockout mice is associated with increased IL-2.
11	12441072	STAT6 (signal transducers and activators of transcription 6)-deficient (STAT6-/-) mice have defects in IL-4- and IL-13-mediated functions and thus have a reduced T(H)2-mediated immune response.
12	12441072	Lymphocytes from both vaccinated and mock-vaccinated STAT6-/- mice secreted higher amounts of IL-2 than lymphocytes from BALB/c mice, in the presence or absence of stimulation with UV-inactivated HSV-1.
13	12441072	Finally, depletion of IL-2 increased ocular virus replication in STAT6-/- mice to levels similar to that measured in BALB/c mice.
14	12441072	Our results suggest that in the absence of the STAT6 pathway, IL-2-mediated immune responses are up-regulated.
15	12441072	Enhanced clearance of herpes simplex virus type 1 and reduced herpetic eye disease in STAT6 knockout mice is associated with increased IL-2.
16	12441072	STAT6 (signal transducers and activators of transcription 6)-deficient (STAT6-/-) mice have defects in IL-4- and IL-13-mediated functions and thus have a reduced T(H)2-mediated immune response.
17	12441072	Lymphocytes from both vaccinated and mock-vaccinated STAT6-/- mice secreted higher amounts of IL-2 than lymphocytes from BALB/c mice, in the presence or absence of stimulation with UV-inactivated HSV-1.
18	12441072	Finally, depletion of IL-2 increased ocular virus replication in STAT6-/- mice to levels similar to that measured in BALB/c mice.
19	12441072	Our results suggest that in the absence of the STAT6 pathway, IL-2-mediated immune responses are up-regulated.
20	12441072	Enhanced clearance of herpes simplex virus type 1 and reduced herpetic eye disease in STAT6 knockout mice is associated with increased IL-2.
21	12441072	STAT6 (signal transducers and activators of transcription 6)-deficient (STAT6-/-) mice have defects in IL-4- and IL-13-mediated functions and thus have a reduced T(H)2-mediated immune response.
22	12441072	Lymphocytes from both vaccinated and mock-vaccinated STAT6-/- mice secreted higher amounts of IL-2 than lymphocytes from BALB/c mice, in the presence or absence of stimulation with UV-inactivated HSV-1.
23	12441072	Finally, depletion of IL-2 increased ocular virus replication in STAT6-/- mice to levels similar to that measured in BALB/c mice.
24	12441072	Our results suggest that in the absence of the STAT6 pathway, IL-2-mediated immune responses are up-regulated.
25	12441072	Enhanced clearance of herpes simplex virus type 1 and reduced herpetic eye disease in STAT6 knockout mice is associated with increased IL-2.
26	12441072	STAT6 (signal transducers and activators of transcription 6)-deficient (STAT6-/-) mice have defects in IL-4- and IL-13-mediated functions and thus have a reduced T(H)2-mediated immune response.
27	12441072	Lymphocytes from both vaccinated and mock-vaccinated STAT6-/- mice secreted higher amounts of IL-2 than lymphocytes from BALB/c mice, in the presence or absence of stimulation with UV-inactivated HSV-1.
28	12441072	Finally, depletion of IL-2 increased ocular virus replication in STAT6-/- mice to levels similar to that measured in BALB/c mice.
29	12441072	Our results suggest that in the absence of the STAT6 pathway, IL-2-mediated immune responses are up-regulated.
30	14610620	Major mediators of anti-tumor immunity are CD4(+) T(h)1 cells and CD8(+) cytotoxic T lymphocytes (CTLs).
31	14610620	IL-13 is one of the T(h)2 cytokines that has very similar features to IL-4 through sharing some receptor components and Stat6 signal transduction.
32	14610620	It has been thought that IL-13 is not as critical for immune deviation as IL-4 since it cannot directly act on T cells.
33	15687713	In addition to tumor-induced suppression, two genes, the Stat6 and CD1 genes, are also associated with inhibiting tumor-specific immunity, since mice deficient for these genes have dramatically enhanced resistance to metastatic mammary carcinoma.
34	15699483	LFA-1 co-stimulation inhibits T(h)2 differentiation by down-modulating IL-4 responsiveness.
35	15699483	Specifically, CD28 co-stimulation promotes T(h)2 differentiation, whereas leukocyte function-associated antigen-1 (LFA-1) co-stimulation promotes T(h)1 differentiation and inhibits T(h)2 differentiation.
36	15699483	We show that co-stimulation through LFA-1 does not decrease early IL-4 secretion, but rather induces a loss in IL-4 responsiveness.
37	15699483	T cells primed in the context of LFA-1 co-stimulation require a 5-fold increase in the concentration of IL-4 required to drive T(h)2 differentiation, which is not mediated by a loss in IL-4R expression.
38	15699483	To determine whether LFA-1 co-stimulation impacts on proximal signaling from the IL-4R, we first identified a kinetic window where we could separate IL-4-driven T(h)2 differentiation from initial T cell priming.
39	15699483	Proximal IL-4R signaling, as evidenced by tyrosine phosphorylation of signal transducer and activator of transcription-6 (STAT6), was not inhibited by initial co-stimulation through LFA-1, yet these T cells still required higher amounts of IL-4 and corresponding higher levels of STAT6 activation to up-regulate GATA-3 and induce T(h)2 differentiation.
40	15699483	Thus, LFA-1 co-stimulation appears to interfere with GATA-3 expression downstream of STAT6.
41	15699483	These results suggest that LFA-1 co-stimulation functions as a threshold modulator of T(h)2 differentiation, increasing the effective concentration of IL-4 required to drive T(h)2 responses.
42	15699483	LFA-1 co-stimulation inhibits T(h)2 differentiation by down-modulating IL-4 responsiveness.
43	15699483	Specifically, CD28 co-stimulation promotes T(h)2 differentiation, whereas leukocyte function-associated antigen-1 (LFA-1) co-stimulation promotes T(h)1 differentiation and inhibits T(h)2 differentiation.
44	15699483	We show that co-stimulation through LFA-1 does not decrease early IL-4 secretion, but rather induces a loss in IL-4 responsiveness.
45	15699483	T cells primed in the context of LFA-1 co-stimulation require a 5-fold increase in the concentration of IL-4 required to drive T(h)2 differentiation, which is not mediated by a loss in IL-4R expression.
46	15699483	To determine whether LFA-1 co-stimulation impacts on proximal signaling from the IL-4R, we first identified a kinetic window where we could separate IL-4-driven T(h)2 differentiation from initial T cell priming.
47	15699483	Proximal IL-4R signaling, as evidenced by tyrosine phosphorylation of signal transducer and activator of transcription-6 (STAT6), was not inhibited by initial co-stimulation through LFA-1, yet these T cells still required higher amounts of IL-4 and corresponding higher levels of STAT6 activation to up-regulate GATA-3 and induce T(h)2 differentiation.
48	15699483	Thus, LFA-1 co-stimulation appears to interfere with GATA-3 expression downstream of STAT6.
49	15699483	These results suggest that LFA-1 co-stimulation functions as a threshold modulator of T(h)2 differentiation, increasing the effective concentration of IL-4 required to drive T(h)2 responses.
50	15905564	IL-12/23 p40(-/-) and IFN-gamma(-/-) mice, which were able to reject the initial inoculation of IL-4 expressing tumors, failed to mount a sustained systemic response against parental (nontransfected) tumor cells.
51	15905564	Adoptive transfer of TIDCs isolated from vaccinated wild-type, but not IL-12/23 p40(-/-), mice were capable of promoting tumor-specific CTL responses in syngeneic recipient animals.
52	15905564	Interestingly, both STAT4(-/-) and STAT6(-/-) mice failed to reject IL-4-transfected tumors in concert with the reduced capacity of TIDCs to produce IL-12p70 and to promote specific antitumor CTL reactivity.
53	16546102	This study examined whether AD skin can control VV replication, and the role of IL-4 and IL-13 in modulating the human cathelicidin LL-37, an antimicrobial peptide that kills VV.
54	16546102	IL-4/IL-13 enhanced VV replication while downregulating LL-37 in VV-stimulated keratinocytes.
55	16546102	Neutralizing IL-4/IL-13 in AD skin augmented LL-37 and inhibited VV replication.
56	16546102	Cathelicidins were induced via toll-like receptor-3 and were inhibited by IL-4/IL-13 through STAT-6.
57	16585215	CD1d-restricted natural killer T cells can down-regulate tumor immunosurveillance independent of interleukin-4 receptor-signal transducer and activator of transcription 6 or transforming growth factor-beta.
58	16585215	Further, we examined the role of CD4(+) and/or CD8(+) cells by depleting the cells in vivo and measuring CTL activity in vitro.
59	16585215	We also asked the role of interleukin (IL)-4 receptor alpha (IL-4Ralpha)-signal transducer and activator of transcription 6 (STAT6) signaling, including IL-13, and transforming growth factor beta (TGF-beta) by using gene-disrupted mice or treating mice with cytokine antagonists.
60	16585215	Further studies suggested that the rejection of tumor in CD1d KO mice was dependent on CD8(+) lymphocytes.
61	16585215	Distinct from other murine tumor models, the negative regulation induced by CD1d-restricted NKT cells was not dependent on IL-4Ralpha-STAT6 signaling, including IL-13, or on TGF-beta.
62	16585215	CD1d-restricted natural killer T cells can down-regulate tumor immunosurveillance independent of interleukin-4 receptor-signal transducer and activator of transcription 6 or transforming growth factor-beta.
63	16585215	Further, we examined the role of CD4(+) and/or CD8(+) cells by depleting the cells in vivo and measuring CTL activity in vitro.
64	16585215	We also asked the role of interleukin (IL)-4 receptor alpha (IL-4Ralpha)-signal transducer and activator of transcription 6 (STAT6) signaling, including IL-13, and transforming growth factor beta (TGF-beta) by using gene-disrupted mice or treating mice with cytokine antagonists.
65	16585215	Further studies suggested that the rejection of tumor in CD1d KO mice was dependent on CD8(+) lymphocytes.
66	16585215	Distinct from other murine tumor models, the negative regulation induced by CD1d-restricted NKT cells was not dependent on IL-4Ralpha-STAT6 signaling, including IL-13, or on TGF-beta.
67	17023392	N-linked glycosylation of IL-13R alpha2 is essential for optimal IL-13 inhibitory activity.
68	17023392	The extracellular domain of IL-13R alpha2 (ECD alpha2) could be cleaved, which serves as a decoy receptor.
69	17023392	The purified glycosylated ECD alpha2 efficiently inhibited IL-13-induced STAT6 phosphorylation in immune and Hodgkin's lymphoma cell lines, IL-13 binding, and cytotoxicity of IL-13 cytotoxin in various cancer cell lines.
70	17023392	ECD alpha2 did not inhibit IL-4-induced STAT6 phosphorylation, indicating that inhibitory effects of ECD alpha2 are receptor specific.
71	17023392	N-linked glycosylation of IL-13R alpha2 is essential for optimal IL-13 inhibitory activity.
72	17023392	The extracellular domain of IL-13R alpha2 (ECD alpha2) could be cleaved, which serves as a decoy receptor.
73	17023392	The purified glycosylated ECD alpha2 efficiently inhibited IL-13-induced STAT6 phosphorylation in immune and Hodgkin's lymphoma cell lines, IL-13 binding, and cytotoxicity of IL-13 cytotoxin in various cancer cell lines.
74	17023392	ECD alpha2 did not inhibit IL-4-induced STAT6 phosphorylation, indicating that inhibitory effects of ECD alpha2 are receptor specific.
75	17092436	IgE levels in serum and IL-4/IL-13 levels in BALF were determined by ELISA.
76	17092436	Expressions of STAT6 and NF-kappaB in lung were determined by immunohistochemistry staining.
77	17092436	Significant reductions of eosinophil infiltration and levels of IL-4 and IL-13 in BALF were observed after vaccination.
78	17092436	Further more, DNA vaccination inhibited STAT6 and NF-kappaB expression in lung tissue in Der p 2-immunized mice.
79	17092436	IgE levels in serum and IL-4/IL-13 levels in BALF were determined by ELISA.
80	17092436	Expressions of STAT6 and NF-kappaB in lung were determined by immunohistochemistry staining.
81	17092436	Significant reductions of eosinophil infiltration and levels of IL-4 and IL-13 in BALF were observed after vaccination.
82	17092436	Further more, DNA vaccination inhibited STAT6 and NF-kappaB expression in lung tissue in Der p 2-immunized mice.
83	18566382	Coligation of the hepatitis C virus receptor CD81 with CD28 primes naive T lymphocytes to acquire type 2 effector function.
84	18566382	In this study, we describe for the first time that coligation of the tetraspanins CD81, CD82, or CD9 with the costimulatory molecule CD28 in vitro leads to proliferation of naive T cells.
85	18566382	When activated through this pathway, both CD4+ and CD8+ naive T cells differentiate into type 2 effector cells, which produce IL-4, IL-5, IL-13, and IL-10, together with IL-2 and TNF-alpha, but little to no IFN-gamma.
86	18566382	These effector cells descend from precursors that display early and strong production of IL-4, STAT6 phosphorylation, and up-regulation of the transcription factor GATA-3, suggesting a direct skewing toward Th2 differentiation without a Th0 intermediate.
87	18566382	The hepatitis C virus envelope protein E2 is the only ligand known for CD81.
88	19338001	Our results have revealed an unexpected dichotomy in the effector phase following cancer vaccination where anti-tumor immunity is mediated via a STAT6 and IL-4-dependent pathway, whereas autoimmune pathology is mediated via STAT4 through a mechanism that relies partially on IFN-gamma.
89	23933364	IL-4 and IL-13 mediated down-regulation of CD8 expression levels can dampen anti-viral CD8⁺ T cell avidity following HIV-1 recombinant pox viral vaccination.
90	23933364	We have shown that mucosal HIV-1 recombinant pox viral vaccination can induce high, avidity HIV-specific CD8(+) T cells with reduced interleukin (IL)-4 and IL-13 expression compared to, systemic vaccine delivery.
91	23933364	Out of a panel of T cell avidity markers tested, only CD8 expression levels were found to be enhanced on, KdGag197-205 (HIV)-specific CD8(+) T cells obtained from IL-13(-/-), IL-4(-/-) and signal transducer and, activator of transcription of 6 (STAT6)(-/-) mice compared to wild-type (WT) controls following, vaccination.
92	23933364	Elevated CD8 expression levels in this instance also correlated with polyfunctionality, (interferon (IFN)-γ, tumour necorsis factor (TNF)-α and IL-2 production) and the avidity of HIVspecific CD8(+) T cells.
93	23933364	IL-13Rα2) vaccines significantly enhanced CD8 expression levels on HIV-specific CD8(+), T cells, which correlated with avidity.
94	23933364	Using anti-CD8 antibodies that blocked CD8 availability on CD8(+), T cells, it was established that CD8 played an important role in increasing HIV-specific CD8(+) T cell avidity and polyfunctionality in IL-4(-/-), IL-13(-/-) and STAT6(-/-) mice compared to WT controls, following vaccination.
95	23933364	Collectively, our data demonstrate that IL-4 and IL-13 dampen CD8 expression levels on anti-viral CD8(+) T cells, which can down-regulate anti-viral CD8(+) T cell avidity and, polyfunctionality following HIV-1 recombinant pox viral vaccination.
96	23933364	IL-4 and IL-13 mediated down-regulation of CD8 expression levels can dampen anti-viral CD8⁺ T cell avidity following HIV-1 recombinant pox viral vaccination.
97	23933364	We have shown that mucosal HIV-1 recombinant pox viral vaccination can induce high, avidity HIV-specific CD8(+) T cells with reduced interleukin (IL)-4 and IL-13 expression compared to, systemic vaccine delivery.
98	23933364	Out of a panel of T cell avidity markers tested, only CD8 expression levels were found to be enhanced on, KdGag197-205 (HIV)-specific CD8(+) T cells obtained from IL-13(-/-), IL-4(-/-) and signal transducer and, activator of transcription of 6 (STAT6)(-/-) mice compared to wild-type (WT) controls following, vaccination.
99	23933364	Elevated CD8 expression levels in this instance also correlated with polyfunctionality, (interferon (IFN)-γ, tumour necorsis factor (TNF)-α and IL-2 production) and the avidity of HIVspecific CD8(+) T cells.
100	23933364	IL-13Rα2) vaccines significantly enhanced CD8 expression levels on HIV-specific CD8(+), T cells, which correlated with avidity.
101	23933364	Using anti-CD8 antibodies that blocked CD8 availability on CD8(+), T cells, it was established that CD8 played an important role in increasing HIV-specific CD8(+) T cell avidity and polyfunctionality in IL-4(-/-), IL-13(-/-) and STAT6(-/-) mice compared to WT controls, following vaccination.
102	23933364	Collectively, our data demonstrate that IL-4 and IL-13 dampen CD8 expression levels on anti-viral CD8(+) T cells, which can down-regulate anti-viral CD8(+) T cell avidity and, polyfunctionality following HIV-1 recombinant pox viral vaccination.
103	24967908	Arg1 expression was amplified by, but did not require, IL-4, and required de novo synthesis of unknown protein(s).
104	24967908	Analysis of growth factors and their signaling pathways revealed that the Fibroblast Growth Factor Receptor 1 (FGFR-1) and Insulin-like Growth Factor 1 Receptor (IGF-1R) and a number of downstream signaling proteins were activated in splenic macrophages isolated from hamsters infected with L. donovani.
105	24967908	Recombinant FGF-2 and IGF-1 increased the expression of arg1 in L. donovani infected hamster macrophages, and this induction was augmented by IL-4.
106	24967908	Inhibition of FGFR-1 and IGF-1R decreased arg1 expression and restricted L. donovani replication in both in vitro and ex vivo models of infection.
107	24967908	STAT6 was activated in infected macrophages exposed to either FGF-2 or IGF-1, and STAT6 was critical to the FGFR-1- and IGF-1R-mediated expression of arg1.
108	24967908	The converse was also true as inhibition of FGFR-1 and IGF-1R reduced the activation of STAT6 in infected macrophages.
109	24967908	Collectively, these data indicate that the FGFR/IGF-1R and IL-4 signaling pathways converge at STAT6 to promote pathologic arg1 expression and intracellular parasite survival in VL.
110	24968940	We found that helminth infection, characterized by the induction of the cytokine interleukin-4 (IL-4) and the activation of the transcription factor Stat6, reactivated murine γ-herpesvirus infection in vivo.
111	24968940	IL-4 promoted viral replication and blocked the antiviral effects of interferon-γ (IFNγ) by inducing Stat6 binding to the promoter for an important viral transcriptional transactivator.
112	24968940	We found that helminth infection, characterized by the induction of the cytokine interleukin-4 (IL-4) and the activation of the transcription factor Stat6, reactivated murine γ-herpesvirus infection in vivo.
113	24968940	IL-4 promoted viral replication and blocked the antiviral effects of interferon-γ (IFNγ) by inducing Stat6 binding to the promoter for an important viral transcriptional transactivator.
114	25493691	IL-17A expression in HIV-specific CD8 T cells is regulated by IL-4/IL-13 following HIV-1 prime-boost immunization.
115	25493691	Our previous studies have shown that vaccination of IL-4 and IL-13 gene knockout (KO) mice can induce high-avidity HIV K(d)Gag197-205-specific CD8 T cells with better protective efficacy.
116	25493691	In this study, when IL-13, IL-4, STAT6 KO, and wild-type BALB/c mice were prime-boost immunized with an HIV poxviral modality, elevated numbers of IL-17A(+) splenic K(d)Gag197-205-specific CD8 T cells were observed in all the KO mice compared with the wt BALB/c control.
117	25493691	Similarly, when wt BALB/c mice were immunized with IL-13Rα2-adjuvanted HIV vaccines (that transiently inhibited IL-13 activity and induced high-avidity CD8 T cells with enhanced protective efficacy), elevated IL-17A(+) K(d)Gag197-205-specific CD8 T cells were detected both in the lung and the spleen.
118	25493691	However, at the transcriptional level, elevated TGF-β, IL-6, ROR-γt, and IL-17A mRNA copy numbers were mainly detected in IL-4 KO, but not the IL-13 KO mice.
119	25493691	These data suggested that TGF-β, IL-6, ROR-γt, but not IL-23a, played a role in IL-17A regulation in K(d)Gag197-205-specific CD8 T cells.
120	25493691	Collectively, our findings suggest that IL-4 and IL-13 differentially regulate the expression of IL-17A in K(d)Gag197-205-specific CD8 T cells at the transcriptional and translational level, respectively, implicating IL-17A as an indirect modulator of CD8 T cell avidity and protective immunity.
121	25877890	Stimulator of interferon genes (STING) is a cytosolic receptor that senses both exogenous and endogenous cytosolic cyclic dinucleotides (CDNs), activating TBK1/IRF3 (interferon regulatory factor 3), NF-κB (nuclear factor κB), and STAT6 (signal transducer and activator of transcription 6) signaling pathways to induce robust type I interferon and proinflammatory cytokine responses.
122	25877890	CDN ligands were formulated with granulocyte-macrophage colony-stimulating factor (GM-CSF)-producing cellular cancer vaccines--termed STINGVAX--that demonstrated potent in vivo antitumor efficacy in multiple therapeutic models of established cancer.
123	25877890	Tumors from STINGVAX-treated mice demonstrated marked PD-L1 (programmed death ligand 1) up-regulation, which was associated with tumor-infiltrating CD8(+)IFNγ(+) T cells.