Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

IL-6 augments IL-4-induced polarization of primary human macrophages through synergy of STAT3, STAT6 and BATF transcription factors

ABSTRACT: IL-6 augments IL-4-induced polarization of primary human macrophages through synergy of STAT3, STAT6 and BATF transcription factors

PROVIDER: PRJNA509359 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR8310970.fastq.gz	Fastqsanger.gz
	SRR8310980.fastq.gz	Fastqsanger.gz
	SRR8310971.fastq.gz	Fastqsanger.gz
	SRR8310972.fastq.gz	Fastqsanger.gz
	SRR8310973.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 12

Similar Datasets

IL-6 augments IL-4-induced polarization of primary human macrophages through synergy of STAT3, STAT6 and BATF transcription factors

Project description:Here we explored how cytokines of the tumor milieu, interleukin (IL)-6 and IL-4, interact to influence target gene expression in primary human monocyte-derived macrophages (hMDMs). We show that dual stimulation with IL-4 and IL-6 synergistically modified gene expression. Among the synergistically induced genes are several targets with known pro-tumorigenic properties, such as CC-chemokine ligand 18 (CCL18), transforming growth factor alpha (TGFA) or CD274 (programmed cell death 1 ligand 1 (PD-L1)). We found that transcription factors of the signal transducer and activator of transcription (STAT) family, STAT3 and STAT6 bind regulatory regions of synergistically induced genes in close vicinity. STAT3 and STAT6 co-binding further induces the basic leucine zipper ATF-like transcription factor (BATF), which participates in synergistic induction of target gene expression. Functional analyses revealed increased MCF-7 and MDA-MB 231 tumor cell motility in response to conditioned media from co-treated hMDMs compared to cells incubated with media from single cytokine-treated hMDMs. Flow cytometric analysis of T cell populations upon co-culture with hMDMs polarized by different cytokines indicated that dual stimulation promoted immunosuppressive properties of hMDMs in a PD-L1-dependent manner. Analysis of clinical data revealed increased expression of BATF together with TAM markers in tumor stroma of breast cancer patients as compared to normal breast tissue stroma. Collectively, our findings suggest that IL-4 and IL-6 cooperate to alter the human macrophage transcriptome, endowing hMDMs with pro-tumorigenic properties.

2018-12-11 | GSE123603 | GEO

Genome-wide detection of STAT6 binding sites in IL-4 treated naive human CD4+ T cells

Project description:STAT6 is a major transcription factor driving the polarization of Th2 cells in response to IL-4. STAT6 is phosphorylated by Jak1 and Jak3 kinases at the IL-4 receptor, after which phosphorylated STAT6 forms a homodimer and translocates into the nucleus. There STAT6 binds to specific DNA sequences, regulating the transcription of its target genes. Here we have analyzed on a genome wide level the STAT6 binding sites, after 1h and 4h of IL-4 induction, in naive human CD4+ T cells. Keywords: SRA Altogether 5 samples from 1 biological replicate were analyzed. Activated and IL-4 treated samples were compared to only activated or untreated samples to identify unique STAT6 binding sites after IL-4 induction.

2010-06-25 | E-GEOD-17850 | biostudies-arrayexpress

Comparison of gene expression profiles of naÃ¯ve and in vitro effector CD8+ T cells from wild-type and BATF-/- mice

Project description:The transcription factor BATF is required for Th17 and TFH differentiation. Here, we show that BATF also has a fundamental role in regulating effector CD8+ T cell differentiation. BATF-deficient CD8+ T cells show profound defects in effector expansion and undergo proliferative and metabolic catastrophe early after antigen encounter. BATF, together with IRF4 and Jun proteins, binds to and promotes early expression of genes encoding lineage-specific transcription-factors (T-bet and Blimp-1) and cytokine receptors, while paradoxically repressing genes encoding effector molecules (IFNg and granzyme B). Thus, BATF amplifies TCR-dependent transcription factor expression and augments inflammatory signal propagation but restrains effector gene expression. This checkpoint prevents irreversible commitment to an effector fate until a critical threshold of downstream transcriptional activity has been achieved. P14 TCR transgenic CD8+ T cells from wild-type or BATF-/- mice were examined either as naÃ¯ve cells or after 3 days of in vitro stimulation with antibodies to CD3 and CD28 in the presence of IL-2

2014-03-02 | E-GEOD-54215 | biostudies-arrayexpress

Genome-wide analysis of STAT6 target genes in IL-4 treated human cord blood CD4+ cells

Project description:STAT6 is a major transcription factor driving the polarization of Th2 cells in response to cytokine IL-4. Here we have analyzed on a genome wide level the STAT6 mediated gene expression after IL-4 induction in naive human CD4+ T cells. RNAi mediated STAT6 knockdown was used to reveal the genes specifically regulated by STAT6. Total RNA from STAT6 siRNA treated cord blood CD4+ T cells 12, 24, 48 or 72 hours after culturing the cells in activating (antiCD3+antiCD28) plus or minus IL-4 conditions was compared to total RNA from nonspecific control siRNA treated cells. All together 18 samples were analyzed and 3 biological replicates of the culture were performed for a total of 54 samples.

2010-07-29 | E-GEOD-17851 | biostudies-arrayexpress

Genome-wide detection of STAT6 binding sites in IL-4 treated naive human CD4+ T cells

2010-06-25 | GSE17850 | GEO

Genome-wide analysis of STAT6 target genes in IL-4 treated human cord blood CD4+ cells

2010-06-25 | GSE17851 | GEO

Identification of novel STAT6-regulated proteins in mouse B cells by comparative transcriptome and proteome analysis

Project description:IL-4/STAT6-regulated transcriptome and proteome were compared in primary B cells isolated from wild-type and STAT6-deficient mice. B cells were purified from the spleen and stimulated in vitro with anti-CD40 and LPS or anti-IgM-F(ab)2 in the presence or absence of IL-4. Transcriptome analysis was performed with oligonucleotide microarrays. Global relative quantification of proteins was achieved by gel-enhanced label-free liquid chromatography/mass spectrometry (LC/MS). Hierarchical clustering and principal component analysis revealed that IL-4-induced changes of the transcriptome were almost completely dependent on STAT6. In contrast, the quantitative proteome analysis revealed that the expression of many IL-4-regulated proteins changes even in the absence of STAT6. The top 75 proteins with changes in abundance levels induced by IL-4 in a STAT6-dependent manner were also found to be regulated at the transcriptional level. Most of these proteins were not previously known to be regulated by STAT6 in B cells. We confirmed the MS-based quantitative proteome data by flow cytometric and Western blot analysis of selected proteins. This study provides a framework for further functional characterization of STAT6-regulated proteins in B cells that might be involved in germinal center formation and class switch recombination.

2017-03-06 | PXD005224 | Pride

T-bet and STAT6 Coordinately Suppress the Development of IL-9-mediated Atopic Dermatitis-like Skin Inflammation in Mice

Project description:T-bet and STAT6 are critical factors for helper T cell differentiation in humans and mice. Additionally, polymorphisms in TBX21 (T-bet) and STAT6 are associated with the susceptibility of allergic diseases. However, precise mechanisms of the reciprocal regulation between T-bet and STAT6 in allergy remain unclear. To determine the reciprocal regulation in vivo, we investigated the phenotype of T-bet/STAT6 double-deficient (T-bet-/- STAT6-/-) mice. Unexpectedly, T-bet-/- STAT6-/- mice but not T-bet-/- mice or STAT6-/- mice spontaneously developed severe dermatitis. Not only eosinophils and mast cells but also CD4+ T cells infiltrated into the skin of T-bet-/- STAT6-/- mice. Adoptive transfer of CD4+ T cells of T-bet-/- STAT6-/- mice into SCID mice induced the accumulation of eosinophils and mast cells in the skin, while depletion of CD4+ T cells ameliorated the dermatitis in T-bet-/- STAT6-/- mice. Comprehensive transcriptome analyses revealed that IL-9 expression was enhanced in T-bet-/- STAT6-/- CD4+ T cells. Indeed, IL-9 neutralization ameliorated the dermatitis in T-bet-/- STAT6-/- mice. Importantly, T-bet-/- STAT6-/- CD4+ T cells expressed functional TSLP receptor and produced large amounts of IL-9 upon TSLP stimulation. These results indicate that T-bet and STAT6 suppress atopic dermatitis-like skin inflammation, possibly by inhibiting TSLP-dependent IL-9 production in CD4+ T cells.

2020-08-15 | GSE156288 | GEO

IL-4-BATF signaling directly modulates IL-9 producing mucosal mast cell (MMC9) function in experimental food allergy

Project description:IL-4-BATF signaling directly modulates IL-9 producing mucosal mast cell (MMC9) function in experimental food allergy

2021-07-03 | GSE179304 | GEO

Bach2-Batf interactions control Th2-type immune responses by regulating the IL-4 amplification loop

Project description:Although Bach2 plays an important role in regulating the Th2-type immune response, the underlying molecular mechanisms remain unclear. We herein demonstrate that Bach2 associates with Batf and binds to the regulatory regions of the Th2 cytokine gene loci. The Bach2-Batf complex antagonizes the recruitment of the Batf-Irf4 complex to AP-1 motifs and suppresses Th2 cytokine production. Furthermore, we found that Bach2 regulates the Batf and Batf3 expressions via two distinct pathways. First, Bach2 suppresses the maintenance of the Batf and Batf3 expression through the inhibition of IL-4 production. Second, the Bach2-Batf complex directly binds to the Batf and Batf3 gene loci and reduces transcription by interfering with the Batf-Irf4 complex. These findings suggest that IL-4 and Batf form a positive feedback amplification loop to induce Th2 cell differentiation and the subsequent Th2-type immune response, and Bach2-Batf interactions are required to prevent an excessive Th2 response.

2016-11-14 | GSE65084 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data