Expression Data of Treg and Tconv Cells from FoxP3-GFP Chimeric and FoxP3-ires-GFP B6 and NOD Mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: CBDM Lab
PROVIDER: E-GEOD-37605 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:The aim of this study was to quantify the impact of chimeric Foxp3-GFP protein on the Treg cell transcriptional program.
2012-04-27 | GSE37605 | GEO
Project description:Analysis of Foxp3(+)epigenetics(-) T cells, Foxp3(-)epigenetics(+) T cells, and Foxp3(+)epigenetics(+) T cells. Results indicate regulatory T cell (Treg) ontogenesis requires two independent processes, expression of the transcription factor Foxp3 and establishment of Treg epigenetic programs induced by T cell receptor (TCR) stimulation. GFP+CD4+ and GFP-CD4+ splenocytes were sorted from DEREG and DEREG/Scurfy mice. These cells were activated with anti-CD3/CD28 antibodies, and then transduced with Foxp3-expressing retrovirus (pGCSamIN, NGFR marker). NGFR+ T cells sorted were subjected to microarray analysis (Affymetrix, mouse genome 430 2.0 array). To normalize the experimental conditions, Tregs (GFP+ T cells from DEREG) and Tconv (GFP- T cells from DEREG) were also activated and transduced with empty vector. Two replicates each.
2012-11-05 | E-GEOD-25252 | biostudies-arrayexpress
Project description:The transcription factor FoxP3 partakes dominantly in the specification and function of FoxP3+ CD4+ T regulatory cells (Tregs), but is neither strictly necessary nor sufficient to determine the characteristic Treg transcriptional signature. Computational network inference and experimental testing assessed the contribution of several other transcription factors (TFs). Enforced expression of Helios or Xbp1 elicited specific signatures, but Eos, Irf4, Satb1, Lef1 and Gata1 elicited exactly the same outcome, synergizing with FoxP3 to activate most of the Treg signature, including key TFs, and enhancing FoxP3 occupancy at its genomic targets. Conversely, the Treg signature was robust to inactivation of any single cofactor. A redundant genetic switch thus locks-in the Treg phenotype, a model which accounts for several aspects of Treg physiology, differentiation and stability. To study the impact of FoxP3 and its candidate cofactors (Eos, Gata1, Helios, Irf4, Lef1, Satb1, Xbp1) on the expression of the Treg transcriptional signature, CD4+ conventional T cells (Tconv) activated with anti-CD3+CD28 beads were retrovirally transduced with cDNAs encoding FOXP3, candidate TFs, or a combination of FOXP3 and candidate TFs. After 3 days in culture, the transduced cells were sorted into Trizol, and RNA was purified, labeled and hybridized to Affymetrix arrays.
2012-08-23 | E-GEOD-40274 | biostudies-arrayexpress
Project description:Several clinical trials have shown anti-CD3 treatment to be a promising therapy for autoimmune diabetes, but its mechanism of action remains unclear. Foxp3+ regulatory T (Treg) cells are likely to be involved, and we have shown a strong effect of anti-CD3 on homeostatic control of CD4+ FoxP3+ regulatory T (Treg) cells. To analyze the early consequences of anti-CD3 treatment, we sorted and profiled Treg and conventional CD4+ T (Tconv) cells in the first hours and days after anti-CD3 treatment of NOD mice. In practice, NOD mice carrying the Foxp3-GFP reporter were treated with anti-CD3 mAb KT3 (50 ug iv) and CD4+ T cells were sorted from pooled spleen and lymph nodes after 2, 8, 24 and 72 hrs, separating Treg and Tconv cells on the basis of GFP expression. Anti-CD3 treatment led to a transient transcriptional response, terminating faster than most antigen-induced responses. Most transcripts were similarly induced in Treg and Tconv cells, but several were differential, in particular those encoding the IL7 receptor (IL7R) and transcription factors Id2/3 and Gfi1, upregulated in Treg but repressed in Tconv cells. In parallel experiments, we tested the effect of soluble anti-CD3 added to cultures of fresh splenocytes, sorting Treg and Tconv cells at the same time points. Many of the anti-CD3 elicited changes, and of the differential response observed in vivo, were also observed in vitro. Two independent replicate series; Treg and Tconv samples abbreviated TR and TC, respectively. Keywords: Transcriptional activation, TCR All gene expression profiles were obtained from highly purified T cell populations sorted by flow cytometry. RNA from 5 x 104 cells was amplified, labeled, and hybridized to Affymetrix ST1.0 Gene arrays. Raw data were preprocessed with the RMA algorithm in GenePattern, and averaged expression values were used for analysis.
2013-07-01 | E-GEOD-48210 | biostudies-arrayexpress
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:Co-stimulatory molecules of the CD28 family on T lymphocytes integrate cues from innate immune system sensors, and modulate activation responses in conventional CD4+ T cells (Tconv) and their FoxP3+ regulatory counterparts (Treg). To better understand how costimulatory and co-inhibitory signals might be integrated, we profiled the changes in gene expression elicited in the hours and days after engagement of Treg and Tconv by anti-CD3 and either anti-CD28, -CTLA4, -ICOS, -PD1, -BTLA or -CD80. Total CD4+ T cells were stimulated by anti-CD3 and either anti-CD28, -CTLA4, -ICOS, -PD1, -BTLA or -CD80 antibodies for 1, 4, 20 and 48 hrs and Tconv and Treg were separated by flowcytometry. The 1 and 4 hr lysates were pooled [the 'early' samples] before RNA purification and profiling, as were the 20 and 48 hr samples [the 'late' samples] (note; for Treg cells, only the 20 hr sample was used). RNA was amplified, labeled and hybridized to Mouse Gene 1.0 ST arrays with the data generation and quality control pipeline of 19 the Immunological Genome Project (www.immgen.org), in biological triplicates (duplicates only for ICOS and CD80). Raw data were background-corrected and normalized using the RMA algorithm.
2012-11-15 | E-GEOD-42276 | biostudies-arrayexpress
Project description:There is much controversy about the role of T-regulatory cells (Treg) in human colon cancer. High densities of tumor-infiltrating Treg can correlate with better or worse clinical outcomes depending on the sutdy. Treg have potent anti-inflammatory functions that have been shown to control cancer progression. However, Treg isolated from patient with colon cancer or in mouse models of polyposis do not have the ability to suppress inflammation and instead promote cancer. Gene expression was preformed to determine differences between Treg isolated from healthy mice and Treg isolated from polyp-ridden mice. Treg (CD4+Foxp3-GFP+) and CD4+ non-Treg (CD4+Foxp3-GFP-) were isolated from various organs of healthy Foxp3-GFP reporter mice or polyp-ridden Foxp3-GFPxAPCΔ468 reporter mice
2012-09-30 | E-GEOD-41229 | biostudies-arrayexpress
Project description:The transcription factor FoxP3 partakes dominantly in the specification and function of FoxP3+ CD4+ T regulatory cells (Tregs), but is neither strictly necessary nor sufficient to determine the characteristic Treg transcriptional signature. Computational network inference and experimental testing assessed the contribution of several other transcription factors (TFs). Enforced expression of Helios or Xbp1 elicited specific signatures, but Eos, Irf4, Satb1, Lef1 and Gata1 elicited exactly the same outcome, synergizing with FoxP3 to activate most of the Treg signature, including key TFs, and enhancing FoxP3 occupancy at its genomic targets. Conversely, the Treg signature was robust to inactivation of any single cofactor. A redundant genetic switch thus locks-in the Treg phenotype, a model which accounts for several aspects of Treg physiology, differentiation and stability. To study the impact of deficiency of candidate FoxP3 cofactors (Xbp1, Eos, Gata1) on the expression of the Treg transcriptional signature, gene expression profiles were generated from purified splenic CD4+CD25hi Tregs of these mutant or knockout mice and their wildtype littermates.
2012-08-23 | E-GEOD-40273 | biostudies-arrayexpress
Project description:Here, we report on experiments in double-transgenic mice, in which RFP is expressed in all Foxp3+ Treg cells, whereas Foxp3-dependent GFP expression is exclusively confined to intrathymically induced Foxp3+ Treg cells. This novel molecular genetic tool enabled us to faithfully track and characterize naturally induced Treg cells of intrathymic (RFP+GFP+) and extrathymic (RFP+GFPM-bM-^HM-^R) origin in otherwise unmanipulated mice. These experiments directly demonstrate that extrathymically induced Treg cells substantially contribute to the overall pool of mature Foxp3+ Treg cells residing in peripheral lymphoid tissues of steady-state mice. Furthermore, we provide evidence that intra- and extrathymically induced Foxp3+ Treg cells represent distinct phenotypic and functional sublineages. CD4+CD25+ RFP+GFP- and CD4+CD25+ RFP+GFP+ T cells from pooled lymph nodes and pooled spleens of 20 mice were FACS sorted for RNA extraction and hybridization on Affymetrix microarrays in duplicates.
2014-07-09 | E-GEOD-59202 | biostudies-arrayexpress
Project description:Gene expression profiling of Bone Marrow FoxP3+ Treg cells. Glatman Zaretsky et al. revealed an unexpected role for Tregs in plasma cell biology. Here we determined the gene-expression profile of this new subset of FoxP3+ Treg cell, which express high levels of Treg effector molecules, similar to other non-lymphoid tissue Tregs. Gene-profiling of BM Tregs. Bone marrow Treg cells (30k) (gfp+CD25hiCD4+TCRβ+) (dump negative: CD19-CD8α-TCRγδ-CD11b-CD11c-NK1.1-Gr-1-Ter-119-) were triple-sorted from pools of two to three reporter mice (C57BL/6 Foxp3-IRES-gfp, 9 week-old males) into trizol per ImmGen SOP. RNA was amplified, labeled and hybridized to Affymetrix Mouse Gene 1.0 ST Arrays (Expression Analysis)
2015-12-23 | E-GEOD-76264 | biostudies-arrayexpress