Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA183430 | ENA |
REPOSITORIES: ENA
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Project description:Objective. TNF? is a potent pro-inflammatory cytokine playing a pivotal role in several autoimmune diseases. Neutralizing TNF? inhibits T cell proliferation and IFN? production, and enhances suppressive capacity of regulatory T cells (Treg). Little is known about the mechanism of TNF? blocking agents on naïve T cell differentiation. Methods. Naïve CD4+ T cells were activated by dendritic cells (DC) in presence or absence of anti-TNF? agents. T cell polarization and activation was assessed during T cell differentiation. In addition, whole genome gene expression analysis was performed on anti-TNF?-treated T cells. Results. Neutralizing TNF? during priming of naïve CD4+ T cells by DC favors development of IL-10+ T helper (Th) cells at the expense of IFN? induction. TNF? inhibits IL-10 via TNFRII, which becomes expressed after naïve T cell activation. While initial CD4+ T cell activation was not affected, neutralization of TNF? negatively affected later stages of T cell priming by counteracting full T cell activation and survival. Whole genome gene expression analysis revealed a regulatory gene profile of anti-TNF?-treated T cells. Indeed, neutralizing TNF? during naïve T cell priming enhanced the suppressive function of anti-TNF?-treated T cells. Conclusion. Inhibition of TNF?–TNFRII interaction affects late stage effector T cell development and shifts the balance of Th cell differentiation towards IL-10 expressing regulatory T cells, which may be one of the beneficial mechanisms in TNF? blocking therapies. Naïve CD4+ T cells were CFSE labeled and co-cultured for 13 days with allogeneic dendritic cells in the presence or absence of anti-TNF? agents. After 13 days, the CFSElow T cells were FACS sorted. Samples were generated from three independent donors.
2014-06-25 | E-GEOD-42812 | biostudies-arrayexpress
Project description:Objective. TNFα is a potent pro-inflammatory cytokine playing a pivotal role in several autoimmune diseases. Neutralizing TNFα inhibits T cell proliferation and IFNγ production, and enhances suppressive capacity of regulatory T cells (Treg). Little is known about the mechanism of TNFα blocking agents on naïve T cell differentiation. Methods. Naïve CD4+ T cells were activated by dendritic cells (DC) in presence or absence of anti-TNFα agents. T cell polarization and activation was assessed during T cell differentiation. In addition, whole genome gene expression analysis was performed on anti-TNFα-treated T cells. Results. Neutralizing TNFα during priming of naïve CD4+ T cells by DC favors development of IL-10+ T helper (Th) cells at the expense of IFNγ induction. TNFα inhibits IL-10 via TNFRII, which becomes expressed after naïve T cell activation. While initial CD4+ T cell activation was not affected, neutralization of TNFα negatively affected later stages of T cell priming by counteracting full T cell activation and survival. Whole genome gene expression analysis revealed a regulatory gene profile of anti-TNFα-treated T cells. Indeed, neutralizing TNFα during naïve T cell priming enhanced the suppressive function of anti-TNFα-treated T cells. Conclusion. Inhibition of TNFα–TNFRII interaction affects late stage effector T cell development and shifts the balance of Th cell differentiation towards IL-10 expressing regulatory T cells, which may be one of the beneficial mechanisms in TNFα blocking therapies.
2014-06-25 | GSE42812 | GEO
Project description:Genomic expression profiling of TNFalpha treated BDC2.5 diabetogenic CD4+ T Cells
| PRJNA108179 | ENA
Project description:Transcriptome profiling of control and TNFalpha treated HepG2 cells
| PRJNA113449 | ENA
Project description:Tumor necrosis factor alpha (TNFalpha) plays an important role in immune regulation, inflammation, and autoimmunity. Chronic TNFalpha exposure has been shown to down-modulate T cell responses. In a mouse T cell hybridoma model, TNFalpha attenuated T cell receptor (TCR) signaling. We have confirmed that chronic TNFalpha and anti-TNFalpha exposure suppressed and increased T cell responses in BDC2.5 CD4+ T cells, respectively. The goal of this study is to analyze global transcriptional alterations resulting from TNFalpha treatment on TCR signaling pathways using cDNA microarrays. We found that genes involved in functional categories including T cell signaling, cell cycle, proliferation, ubiquitination, cytokine synthesis, calcium signaling, and apoptosis were modulated. Genes such as ubiquitin family genes, cytokine inducible SH2-containing genes, cyclin-dependent kinase inhibitors p21, p57, calmodulin family genes (calmodulin -V1, -V2, and ?V3) and calcium channel voltage- dependent, N type alpha1B subunit (CaV2.2) were induced by TNFalpha, while Vav2, Rho GTPase activating protein, calcium channel voltage dependent, L type alpha 1C subunit (CaV1.2), interleukin-1 (IL) receptor-associated kinase 1, and -V2 (IRAK-1and -2) and IL enhancer binding factor 3 were reduced by TNFalpha. Genes such as CaV1.2 and proliferating cell nuclear antigen, repressed by TNFalpha, were induced by anti-TNF treatment. Further, we showed that chronic TNFalpha exposure impaired NF-kappaB and AP-1 transactivation activity, leading to T cell unresponsiveness. Thus, our results present a detailed picture of transcriptional programs affected by chronic TNFalpha exposure, and provide candidate target genes, which may function to mediate TNFalpha induced T cell unresponsiveness. Set of arrays that are part of repeated experiments Keywords: Biological Replicate The experiments addressed the effect of TNF exposure. 8-12-week-old NOD.BDC2.5 transgenic mice were injected i.p. with PBS or 3 ug murine TNFalpha; on alternate days for three weeks. At day 24 of treatment, suspensions of LNs and/or splenocytes were stimulated with the indicated concentration of the mimotope (1047-7 peptide (YVAPVWVRME)) at a density of 7-8 x 106 cells/ml, in a final volume of 1 ml in 24-well plates. After prolonged in vitro culture, cells were harvested 12 hrs post transplantation. CD4+ T cells were purified by labeling of monoclonal Abs of surface markers, Vbeta4-FITC and CD4-PE and enriched by Magnetic beads selection followed by FACS sorting. The purity of CD4+ T cells ranged from 95% to 99% depending on individual CD4 T cells preparation. The data in column represents six independent repeated experiments with half of the slides being reverse replicates. We compared RNA from PBE treated group with TNF treated group without including reference RNA.
2010-06-25 | E-GEOD-10029 | biostudies-arrayexpress
Project description:Transcriptional Profiling of Untreated, HIV-1 Vector-Infected and TNFalpha-treated Jurkat T cells
| PRJNA92031 | ENA
Project description:Histone modification analysis in TGFbeta/TNFalpha treated A549 spheroid cultures
| PRJNA181207 | ENA
Project description:Gene expression analysis in TGFbeta/TNFalpha treated A549 spheroid cultures
| PRJNA181206 | ENA