Expression Data of Treg and Tconv Cells from FoxP3-GFP Chimeric and FoxP3-ires-GFP B6 and NOD Mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE37605 | GEO | 2012/04/27
SECONDARY ACCESSION(S): PRJNA162393
REPOSITORIES: GEO
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Project description:The aim of this study was to quantify the impact of chimeric Foxp3-GFP protein on the Treg cell transcriptional program. Duplicate samples of Tconv (CD3+CD4+GFP-) and Treg (CD3+CD4+GFP+) splenocytes were double-sorted to achieve > 99.0% purity, from 6 weeks old male Foxp3-Fusion-GFP and Foxp3-ires-GFP mice of both B6 and NOD backgrounds. Following cell sorting into Trizol, RNA was purified, labeled and hybridized to Affymetrix arrays.
2012-04-26 | E-GEOD-37605 | biostudies-arrayexpress
Project description:Regulatory T cells (Treg) have been shown to adopt a catabolic metabolic programme with increased capacity for fatty acid oxidation fuelled oxidative phosphorylation (OXPHOS). The role of Foxp3 in this metabolic shift is poorly understood. Here we show that Foxp3 was sufficient to induce a significant increase in the spare respiratory capacity of the cell, the extra OXPHOS capacity available to a cell to meet increased demands on energy in response to work. Foxp3-expressing cells were enhanced in their ability to utilise palmitate for respiration and, in addition, the activity of electron transport complexes I, II and IV were enhanced following Foxp3 expression. Foxp3 also imparts a selective advantage in ATP generation capacity, one that might be exploited as a source of adenosine for functional immunomodulation. In order to explore possible mechanisms for these differences in metabolism we conducted a quantitative proteomics study to compare the contribution of TGFβ and the transcription factor Foxp3 to the Treg proteome. We used quantitative mass spectrometry to examine differences between proteomes of nuclear and cytoplasmic Foxp3-containing CD4+ T cells from various sources with Foxp3- activated CD4 T cells, as well as Treg from human peripheral blood. Gene set enrichment analysis of our proteomic datasets demonstrated that Foxp3 expression is associated with a significant up regulation of several members of the mitochondrial electron transport chain. Not only does Foxp3 influence genes directly concerned with immune function, but also with the energy generating functions of Treg.
2017-02-15 | PXD001906 | Pride
Project description:Natural CD4+FOXP3+ regulatory T (Treg) cells constitute a unique T-cell lineage that plays a pivotal role in maintaining immune homeostasis and immune tolerance. Recent studies provide evidence for the heterogeneity and plasticity of the Treg cell lineage. However, the fate of human Treg cells after loss of FOXP3 expression and the underlying epigenetic mechanisms remain to be fully elucidated. Here, we compared gene expression profiles and histone methylation status on two histone H3 lysine residues (H3K4me3 and H3K27me3) of expanded FOXP3+ and corresponding FOXP3-losing Treg cells. DGE assay showed that human Treg cells down-regulated Treg signature genes, whereas up-regulated a set of Th lineages-associated genes, especially for Th2, such as GATA3, GFI1 and IL13, after in vitro expansion. Furthermore, we found that reprogramming of Treg cells was associated with histone modifications, as shown by decreased abundance of permissive H3K4me3 within down-regulated Treg signature genes, such as FOXP3, CTLA4 and LRRC32 loci, although with no significant changes in H3K27me3 modification. Thus, our results indicate that human Treg cells could convert into a Th-like cells upon in vitro expansion, displaying a gene expression signature dominated by Th2 lineage associated genes, and the histone methylation might contribute to such conversion. mRNA profiles of in-vitro-expanded FOXP3+ Treg and FOXP3-losing Treg cells generated by deep sequencing.
2013-06-06 | E-GEOD-47636 | biostudies-arrayexpress
Project description:The transcription factor Foxp3 is usually considered the master regulator for the CD4+CD25+ "Treg" lineage, which plays a key role in controlling immune and autoimmune responses, and is characterized by a unique transcriptional signature. We have performed a meta-analysis of this signature in Treg cells in several conditions to delineate the elements that can be ascribed to T cell activation, TGFbeta signaling, or Foxp3 itself. We find that these influences synergize to activate many of the signature’s components. Foxp3 and TGFbeta signaling have interconnected relationships, as Foxp3 is induced by TGFbeta while enhancing TGFbeta’s positive feedback loop. Much of the Treg signature cannot be ascribed to Foxp3, as it contains gene clusters that are co-regulated, but cannot be transactivated, by Foxp3. This suggests that the Treg lineage is specified at a higher level of regulation, upstream of Foxp3, which does control some of the lineage’s essential immunoregulatory attributes. Keywords: Cell population comparison
2007-12-04 | GSE7460 | GEO
Project description:Goals and objectives of this study: to identify genes of the Treg signature induced by consitutive expression of GARP or FOXP3 in antigen-specific Th cells with potential role for stabililization & maintenance of the regulatory program. Keywords: T-cell receptor stimulation, gene-regulation, comparative gene expression profiling, cell type comparison, human, regulatory T cells, FOXP3, GARP
2009-04-20 | GSE13234 | GEO
Project description:Goals and objectives of this study: to identify genes of the Treg signature induced by consitutive expression of GARP or FOXP3 in antigen-specific Th cells with potential role for stabililization & maintenance of the regulatory program. Keywords: T-cell receptor stimulation, gene-regulation, comparative gene expression profiling, cell type comparison, human, regulatory T cells, FOXP3, GARP Human alloantigen-specific Treg cells (THU) and Th cells (CD4-39), established and described recently (Ocklenburg et al.. Lab Invest.2006; 86: 724-737), were sitmulated for 3 days with cognate antigen (EBV B cells) and IL2 as described (Ocklenburg et al.. Lab Invest.2006; 86: 724-737) and analyzed using human Affymetrix U133 2.0 in monoplicate. Th cells had been transduced with a retroviral vector containing human GARP (LRRC32) or FOXP3 and an IRES-driven GFP as marker or empty GFP control, sorted for GFP+, expanded as described recently (Ocklenburg et al.. Lab Invest.2006; 86: 724-737), and characterized functially, phenotypically, and genetically as described (WO/2007/113301). Abbreviations: Treg THU d3 = alloantigen-specific Treg cells; GFP d3 = GFP-transduced alloantigen-specific Th cells (CD4-39); FoxP3 d3 = FOXP-transduced alloantigen-specific Th cells (CD4-39); Garp d3 = GARP-transduced alloantigen-specific Th cells (CD4-39); all stimulated for 3 days (=d3) with EBV B cells and IL2.
2009-04-20 | E-GEOD-13234 | biostudies-arrayexpress
Project description:Comparaison of the transcriptomes of WT and Foxp3-deficient regulatory T cells from the spleen of females that carried one mutant Foxp3∆EGFPiCre allele and a second competent Foxp3 allele (Foxp3RFP) that also directed the expression of the red fluorescent protein (RFP) . We then extended these studies to elucidate transcriptional pathways altered upon Rictor deletion in ∆Treg cells that may contribute to their improved regulatory function by analyzing the transcriptome of ∆Treg cells isolated from Foxp3∆EGFPiCre/+Rictor∆/∆ females.
2019-04-08 | GSE129472 | GEO
Project description:Natural CD4+FOXP3+ regulatory T (Treg) cells constitute a unique T-cell lineage that plays a pivotal role in maintaining immune homeostasis and immune tolerance. Recent studies provide evidence for the heterogeneity and plasticity of the Treg cell lineage. However, the fate of human Treg cells after loss of FOXP3 expression and the underlying epigenetic mechanisms remain to be fully elucidated. Here, we compared gene expression profiles and histone methylation status on two histone H3 lysine residues (H3K4me3 and H3K27me3) of expanded FOXP3+ and corresponding FOXP3-losing Treg cells. DGE assay showed that human Treg cells down-regulated Treg signature genes, whereas up-regulated a set of Th lineages-associated genes, especially for Th2, such as GATA3, GFI1 and IL13, after in vitro expansion. Furthermore, we found that reprogramming of Treg cells was associated with histone modifications, as shown by decreased abundance of permissive H3K4me3 within down-regulated Treg signature genes, such as FOXP3, CTLA4 and LRRC32 loci, although with no significant changes in H3K27me3 modification. Thus, our results indicate that human Treg cells could convert into a Th-like cells upon in vitro expansion, displaying a gene expression signature dominated by Th2 lineage associated genes, and the histone methylation might contribute to such conversion.
2013-06-06 | GSE47636 | GEO
Project description:FoxP3 is a central regulator of immunological tolerance, controlling the development and function of regulatory T (Treg) cells. To dissect the complex processes orchestrated by FoxP3, we investigated impacts of three autoimmune disease-associated missense FoxP3 mutations (i.e., I363V, A384T, R397W) through knock-in mutagenesis in mice. We investigated the impacts of these mutations on Treg cell transcriptome by microarray analysis.
2017-08-01 | GSE89654 | GEO
Project description:Differing from the mouse Foxp3 gene that encodes only one protein product, human FOXP3 encodes two major isoforms through alternative splicing – a longer isoform (FOXP3 FL) containing all the coding exons and the other shorter isoform lacking the amino acids encoded by exon 2 (FOXP3 ΔE2). The two isoforms are naturally expressed in humans yet their differences in controlling regulatory T cell phenotype and functionality remains unclear. Here we show that patients expressing only the shorter isoform failed to maintain self-tolerance and developed IPEX syndrome. Mice with Foxp3 exon 2 deletion developed excessive TFH and GC B cell responses and systemic autoimmune disease with anti-dsDNA and anti-nuclear autoantibody production and immune-complex glomerulonephritis. Regulatory T cells expressing FOXP3 ΔE2 were unstable and sufficient to induce autoimmunity when transferred into Tcrb-deficient mice. Mechanistically, FOXP3 ΔE2 isoform allows increased expression of selected cytokines but decreased expression of a set of Foxp3 positive regulators without altered binding to these gene loci. We demonstrate that exon 2 of FOXP3 is required to maintain Treg stability and immune homeostasis.
2022-06-27 | GSE199277 | GEO