Gene expression analysis of iTregs and nTregs
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE39724 | GEO | 2013/07/03
SECONDARY ACCESSION(S): PRJNA171555
REPOSITORIES: GEO
Similar Datasets
Project description:MBP TCR Tg mouse (1B3) generates only iTregs when crossed onto RAGKO background. Tregs from 1B3.RAG mouse were used for gene expression analsysis to determine genes selectively expressed in peripherally generated iTregs iTregs from 1B3.RAG mice (>90% Foxp3+) were run against total Tregs from 1B3 and WT NOD mice. Foxp3- CD4+T cells were used as control from all strains as Tconv. (1B3 denotes MBP-TCR Tg mouse).
2013-07-03 | E-GEOD-39724 | biostudies-arrayexpress
Project description:In this study, we have studied the genes associated with PRMT5 mediated histone methylation (H2R2me2s) in Th1-like iTregs. This particular epigenetic markers is upregulated in Th1 cells, and Th1-like iTregs. Therefore, we wanted to identify the genes H3R2me2s is regulating in Th1-like iTregs as compared to iTregs or Th1 cells. The goal of this sequencing was to identify if H2R2me2s is important for increased suppressive capacity of Th1-like iTregs or not.
2023-12-13 | GSE243686 | GEO
Project description:Thymus-originated tTregs and in vitro induced iTregs are subsets of regulatory T cells. While they share the capacity of immune suppression, their stabilities are different, with iTregs losing their phenotype upon stimulation or under inflammatory milieu. Epigenetic differences, particularly methylation state of Foxp3 CNS2 region, provide an explanation for this shift. Whether additional regulations, including cellular signaling, could directly lead phenotypical instability requires further analysis. Here we show that upon TCR triggering, store-operated calcium entry (SOCE) and NFAT nuclear translocation are blunted in tTregs, yet fully operational in iTregs, similar to Tconvs. On the other hand, tTregs show minimal changes in their chromatin accessibility upon activation, in contrast to iTregs that demonstrate an activated chromatin state with highly accessible T cell activation and inflammation related genes. Assisted by several cofactors, NFAT driven by strong SOCE signaling in iTregs preferentially binds to primed opened T helper (TH) genes, resulting in their activation normally observed only in Tconv activation, ultimately leads to instability. Conversely, suppression of SOCE in iTregs can partially rescue their phenotype. Thus our study adds two new layer, cellular signaling and chromatin accessibility, of understanding in Treg stability, and may provide a path for better clinical applications of Treg cell therapy.
2023-11-01 | GSE246431 | GEO
Project description:Treg dysfunction is associated with a variety of inflammatory diseases. Treg populations are defined by expression of the oligomeric transcription factor FOXP3 and inability to produce IL-2, a cytokine required for T cell maintenance and survival. FOXP3 activity is regulated post-translationally by histone/protein acetyltransferases and histone/protein deacetylases (HDACs). Here, we determined that HDAC3 mediates both the development and function of the two main Treg subsets, thymus-derived Tregs and induced Tregs (iTregs). We determined that HDAC3 and FOXP3 physically interact and that HDAC3 expression markedly reduces Il2 promoter activity. In murine models, conditional deletion of Hdac3 during thymic Treg development restored Treg production of IL-2 and blocked the suppressive function of Tregs. HDAC3-deficient mice died from autoimmunity by 4-6 weeks of age; however, injection of WT FOXP3+ Tregs prolonged survival. Adoptive transfer of Hdac3-deficient Tregs, unlike WT Tregs, did not control T cell proliferation in naive mice and did not prevent allograft rejection or colitis. HDAC3 also regulated the development of iTregs, as HDAC3-deficient conventional T cells were not converted into iTregs under polarizing conditions and produced large amounts of IL-2, IL-6, and IL-17. We conclude that HDAC3 is essential for the normal development and suppressive functions of thymic and peripheral FOXP3+ Tregs. RNA was isolated using RNeasy kits (QIAGEN), and RNA integrity and quantity were analyzed by NanoDrop ND-1000 and Nanochip 2100 Bioanalyzer (Agilent Technologies). Microarray experiments were performed using whole mouse genome oligoarrays (Mouse430a, Affymetrix) and array data analyzed using MAYDAY 2.12 software. Array data were subjected to robust multiarray average (RMA) normalization and analyzed using Student’s t test. Only data with a false discovery rate-adjusted P value of less than 0.05 and at least 2× differential expression were included in the analysis. Data underwent z-score transformation for display.
2015-05-19 | E-GEOD-68991 | biostudies-arrayexpress
Project description:Analysis of differentially expressed genes in CD4+ early iTregs isolated from wild-type and Scd1-deficient mice. The goal of this study was to elucidate the effect of Scd1 on Treg differentation.
2023-02-13 | GSE224839 | GEO
Project description:Regulatory T cells (Tregs) are critical for the maintenance of immune homeostasis and self‑tolerance, and can be therapeutically used for prevention of unwanted immune responses such as allotransplant rejection. Tregs are characterized by the expression of the transcription factor Foxp3, and recent work suggested that epigenetic imprinting of Foxp3 and other Treg‑specific epigenetic signatures genes is crucial for the stabilization of both Foxp3 expression and immunosuppressive properties within Tregs. Lately, Vitamin C was reported to enhance the activity of enzymes of the ten‑eleven‑translocation family, thereby fostering the demethylation of Foxp3 and other Treg‑specific epigenetic signatures genes in developing Tregs. Here, we in vitro generated alloantigen‑specific Foxp3+ Tregs (allo‑iTregs) in presence of vitamin C, and those Tregs showed a pronounced demethylation of Foxp3 and other Treg‑specific epigenetic signatures genes, accompanied with an enhanced stability of Foxp3 expression. However, RNA‑seq analysis revealed an only minor impact of Vitamin C on the transcriptome of allo‑iTregs. Importantly, when being tested in vivo in a highly immunogenic skin transplantation model vitamin C‑treated allo‑iTregs showed a superior suppressive capacity as compared to allo‑iTregs generated in absence of vitamin C. Together, our results might pave the way for the establishment of novel protocols for the in vitro generation of allo‑antigen specific Foxp3+ Tregs for therapeutic usage in transplantation medicine.
2017-06-22 | GSE96960 | GEO
Project description:Treg dysfunction is associated with a variety of inflammatory diseases. Treg populations are defined by expression of the oligomeric transcription factor FOXP3 and inability to produce IL-2, a cytokine required for T cell maintenance and survival. FOXP3 activity is regulated post-translationally by histone/protein acetyltransferases and histone/protein deacetylases (HDACs). Here, we determined that HDAC3 mediates both the development and function of the two main Treg subsets, thymus-derived Tregs and induced Tregs (iTregs). We determined that HDAC3 and FOXP3 physically interact and that HDAC3 expression markedly reduces Il2 promoter activity. In murine models, conditional deletion of Hdac3 during thymic Treg development restored Treg production of IL-2 and blocked the suppressive function of Tregs. HDAC3-deficient mice died from autoimmunity by 4-6 weeks of age; however, injection of WT FOXP3+ Tregs prolonged survival. Adoptive transfer of Hdac3-deficient Tregs, unlike WT Tregs, did not control T cell proliferation in naive mice and did not prevent allograft rejection or colitis. HDAC3 also regulated the development of iTregs, as HDAC3-deficient conventional T cells were not converted into iTregs under polarizing conditions and produced large amounts of IL-2, IL-6, and IL-17. We conclude that HDAC3 is essential for the normal development and suppressive functions of thymic and peripheral FOXP3+ Tregs.
2015-05-19 | GSE68991 | GEO
Project description:Human FOXP3 antisense oligonucleotides (ASOs) target effects in primary iTregs gene expression. Tregs were isolated from human PBMCs from 5 different donors, subjected to one of 4 different treatments: (1) Untreated, (2) Control ASO 792169, (3) FOXP3 ASO 910959, (4) FOXP3 ASO 910956 under either stimulation with aCD3/aCD28 coated beads or left unstimulated.
2024-01-08 | E-MTAB-11589 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE34934: Expression data from BDC2.5 TCR Tg, preselected Rag-/-.B6 and Rag-/-.NOD.H2b thymocytes upon antigenic stimulation GSE34935: Expression data from BDC2.5 TCR Tg thymocytes on B6g7 and NOD background Refer to individual Series
2012-01-10 | E-GEOD-34936 | biostudies-arrayexpress
Project description:Intestinal regulatory T cells consist of at least two distinct populations in flow cytometry. We used single-cell RNA sequencing to determine the transcriptional differences in peripherally and thymically induced Tregs.
2024-04-01 | GSE241605 | GEO