Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Effect anti-TNF-alpha treatment on CD4+ T cell activation

ABSTRACT: The experiment was designed to test how autocrine TNF-alpha impacts human CD4+ T cell activation. Naïve CD4+ T cells from healthy human blood donors were either left unactivated or activated with anti-CD3/anti-CD28 in presence of an isotype control antibody or anti-TNF-alpha antibody. RNA was extracter at 48 hours. Analysis revealed that anti-TNF-alpha treatment prevented upregulation of activation-induced T cell metabolic, signaling and effector molecules.

ORGANISM(S): Homo sapiens

PROVIDER: GSE238247 | GEO | 2024/07/25

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Transcriptional profiling of activated CD4+ memory T cells exposed to anti-TNF and recombinant human TNF-alpha in vitro

Project description:We performed an RNA-seq analysis on FACS-sorted CD4+ memory T cells (Tmem, CD4+CD25-CD45RA-) stimulated in vitro with anti-CD3/CD28 coated beads (1:5), IL-2 (100 U/mL) in the presence of a TNF-alpha inhibitor (Etanercept, ETN, 5 Î¼g/mL) or recombinant human TNF-alpha (rhTNF-alpha, 50 ng/mL) treatment. The cells were cultured for three days at 37Â°C and 5% CO2. On day three Tmem were lysed (Buffer RLT supplemented with DTT, QIAGEN) and RNA extraction was performed (RNeasy Plus Micro kit), followed by sample preparation with TruSeq (polyA) mRNA kits (Illumina), RNA sequencing (carried out by an Illumina HiSeq2500), and the alignment of trimmed fastQ files to GRCh38 human reference genome. We also performed a Quality control (QC). This was done using the tool FastQC FastQC/0.11.3-Java-1.7.0_80. QC metrics were calculated for the aligned reads using Picard-tools picard/1.130-Java-1.7.0_80, CollectRnaSeqMetrics, MarkDuplicates, CollectInsertSize-Metrics and SAMtools/1.2-foss-2015b flagstat. Finally, we carried out a Differential expression gene (DEG) analysis using DESeq2, in order to evaluate the impact of ETN and rhTNF-alpha on Transcriptome profiling of stimulated CD4+ Tmem. Principal Component Analysis (PCA) was carried out to visualise the samples given their entire transcriptome and any remaining batch effects.

2017-12-15 | E-MTAB-5622 | biostudies-arrayexpress

Identification of a transcription factor network that regulates anti-TNF mediated IL-10 expression in human CD4+ T-cells

Project description:CD4+ T-cells are key players in the pathogenesis of rheumatoid arthritis (RA) through potent production of inflammatory mediators including IL-17A, IFNg and TNF. Anti-TNF therapy has revolutionized the treatment of RA and we previously demonstrated that in vitro treatment of human CD4+ T-cells with the anti-TNF monoclonal antibody adalimumab (ADA) promotes anti-inflammatory IL-10 expression in multiple subpopulations of CD4+ T-cells. Here we investigated the transcriptional mechanisms underlying the IL-10 induction by TNF-blockade in in vitro stimulated CD4+ T-cells. CD4+ T-cells were isolated from PBMC of healthy volunteers by magnetic isolation and cultured for 3 days with anti-CD3/CD28 mAb in the absence or presence of anti-TNF. After culture, CD45RA+ cells were depleted and RNA was extracted for gene expression profiling by RNA-seq and cell nuclei were isolated for chromatin accessibility analysis by ATAC-seq. Gene expression analysis of memory CD4+ T-cells showed a distinct gene signature of 183 genes (q-value <0.05) conferred by anti-TNF treatment. Pathway enrichment analysis of the differentially expressed genes revealed multiple pathways related to cytokine signalling and regulation of cytokine production; in particular, IL10 was the most upregulated gene by anti-TNF, while the proinflammatory cytokines and chemokines IFNG, IL9, IL22 and CXCL10 were significantly downregulated (q-value <0.05). Transcription factor (TF) motif analysis at the differentially open chromatin regions after anti-TNF treatment revealed 58 TF motifs, shared by all donors, enriched at the IL10 locus. We identified 7 TF candidates for the anti-TNF mediated regulation of IL-10, which were either differentially expressed or whose locus was differentially accessible upon anti-TNF stimulation. We postulate that this TF network, which includes MAF and PRMD1, drives transcriptional regulation of IL-10 in anti-TNF treated T-cells.

2024-09-25 | GSE216688 | GEO

Molecular mechanism underline immune cell type population shift upon anti-DLL4 treatment

Project description:Molecular mechanism underline immune cell type population shift upon anti-DLL4 treatment C57BL/6 mice were injected with anti-DLL4, or an isotype control antibody as controls. Two weeks later mice were sacrificed, and thymi was harvested from 4 anti-DLL4 and 4 control animals. Total thymocytes, DN cells (CD4-CD8-) and DN1(CD4-CD8- CD44+CD25-) cells were isolated. Samples included in this data set are: 3 Thymocytes-anti-DLL4; 3 Thymocytes-isotype control; 3 DN1-anti-DLL4; 2 DN1-isotype controls; 3 DN-anti-DLL4; 3 DN-isotyoe control.

2012-04-29 | E-GEOD-24296 | biostudies-arrayexpress

Effect of T cell supernatants or cytokines on synovial fibroblasts

Project description:To investigate the effects of soluble factors produced by synovial CD8 T cells, we stimulated human rheumatoid arthritis (RA) synovial fibroblasts with supernatants from synovial fluid CD8 T cells, blood CD8 T cells, or synovial fluid CD4 T cells stimulated with anti-CD3/CD28 antibody-coated beads. For comparison, we stimulated RA synovial fibroblasts with recombinant TNF or interferon-gamma or T cell supernatants pre-incubated with TNF-blocking antibodies.

2022-05-08 | GSE202367 | GEO

In vivo single-cell CRISPR uncovers distinct TNF-α programs in tumor evolution

Project description:The tumor evolution model posits that malignant transformation is preceded by randomly distributed driver mutations in cancer genes, which cause clonal expansions in phenotypically normal tissues. Although clonal expansions can remodel entire tissues1-3, the mechanisms behind why only a small number of clones transform into malignant tumors remain enigmatic. Here, we develop an in vivo single-cell CRISPR strategy to systematically investigate tissue-wide clonal dynamics of the 150 most frequently mutated squamous cell carcinoma genes. We couple ultrasound-guided in utero lentiviral microinjections, single-cell RNA sequencing and guide capture to longitudinally monitor clonal expansions and document their underlying gene programs at single-cell transcriptomic resolution. We uncover a TNF-α signaling module, dependent on TNF receptor 1 and involving macrophages, that acts as a generalizable driver of clonal expansions in epithelial tissues. Conversely, during tumorigenesis, the TNF-α signaling module is downregulated. Instead, we identify a subpopulation of invasive cancer cells that switch to an autocrine TNF-α gene program, associated with epithelial-mesenchymal transition. Finally, we provide in vivo evidence that the autocrine TNF-α gene program is sufficient to mediate invasive properties and show that the TNF-α signature correlates with shorter overall survival in human squamous cell carcinoma patients. Collectively, our study demonstrates the power of applying in vivo single-cell CRISPR screening to mammalian tissues, unveils distinct TNF-α programs in tumor evolution and highlights the importance of understanding the relationship between clonal expansions in epithelia and tumorigenesis.

2024-07-17 | GSE235325 | GEO

Transcriptional profiling of activated CD4+ memory T cells exposed to anti-TNF and recombinant human TNF-alpha in vitro

Project description:Transcriptional profiling of activated CD4+ memory T cells exposed to anti-TNF and recombinant human TNF-alpha in vitro

| PRJEB20297 | ENA

Pathological activation of canonical nuclear-factor kB by synergy of tumor necrosis factor alpha and TNF-like weak inducer of apoptosis in mouse acute colitis

Project description:To test the efficacy of TNFR-Fc and anti-TWEAK mAb treatment alone and in combination Tumor necrosis factor (TNF)-alpha is a major effector in various inflammatory conditions. TNF-like weak inducer of apoptosis (TWEAK) is a member of the TNF superfamily that promotes inflammatory tissue damage through its receptor, FGF-inducible molecule 14 (Fn14). Since both TWEAK and TNF-alpha have been shown to mediate pathological responses through inter-dependent or independent pathways by in vitro, the potential interplay of these pathways was investigated in a mouse colitis model. Acute colitis was induced by rectal injection of trinitrobenzene sulfonic acid (TNBS), with administration of control IgG, TNF receptor (TNFR)-Ig chimeric protein, anti-TWEAK monoclonal antibody, or the combination of TNFR-Ig and anti-TWEAK antibody. On day 4, disease severity was evaluated and gene expression profiling was analyzed using whole colon tissue. Levels of transcript of TWEAK, Fn14 and NF-kB-related molecules were measured in purified colon epithelial cells (ECs). NF-kB activation was investigated with Western blot and immunohistochemical analysis. As a result, activation of the canonical, but not noncanonical NF-kB pathway was the hallmark of inflammatory responses in this model. Inflammation induced upregulation of Fn14 only in ECs but not in other cell types. Combination treatment of TNFR-Ig and anti-TWEAK antibody synergistically reduced disease severity in comparison with the control antibody or single agent treatment. Gene expression profile of the colon indicated downregulation of canonical NF-kB pathway with combination treatment. In conclusion, synergistic activation of canonical NF-kB by TWEAK and TNF-alpha is critical for the induction of inflammatory tissue damage in acute inflammation.

2014-05-30 | GSE53835 | GEO

Gene expression profile of ascites cell samples from patients with advanced ovarian cancer

Project description:We present evidence for an autocrine cytokine network in human ovarian cancer that has paracrine actions on the tumour microenvironment. In experiments using bioinformatics analysis of large gene expression array datasets and ovarian cancer biopsies, we found that the inflammatory cytokines TNF-α and IL-6, the chemokine receptor CXCR4 and its ligand CXCL12, are co-regulated in malignant cells. We named this co-regulation the TNF network. We had access to a unique set of ascites cell samples from patients with advanced ovarian cancer treated with the therapeutic anti-human TNF-α antibody infliximab. Serial samples pre and during treatment were obtained during paracentesis (drainage of ascites fluid for symptomatic relief). In nine of these patients there was sufficient mRNA available for gene expression profile analysis before treatment. The Affymetrix GeneChip Human Genome U133Plus 2.0 arrays were used to define gene expression profiles in each of the ascites cell samples.

2009-12-31 | E-GEOD-18681 | biostudies-arrayexpress

The Co-inhibitory Receptor TIGIT has T cell intrinsic functions

Project description:We compared the gene expression in wild type CD4+ T cells stimulated with agonistic anti-TIGIT 4D4 antibody to that of isotype and TIGIT-deficient (KO) controls.

2011-01-01 | E-MEXP-2847 | biostudies-arrayexpress

Effects of TNF-alpha blocking in sorted Th1 cells from co-cultures of human CD4-positive and CD14-positive cells

Project description:Human CD4+ T cells and CD14+ monocytes from healthy donors were co-cultured with anti-CD3 for three days in the presence or absence of TNF-alpha mAb (Adalimumab). Classical Th1 cells or those generated in the presence of the inhibitor were then sorted and analyzed by full transcriptome microarray analysis.

2019-01-01 | GSE65054 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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