Similar Datasets
Project description:Regulatory T (Treg) cells can facilitate transplant tolerance and attenuate autoimmune- and inflammatory diseases. Therefore, it is clinically relevant to stimulate Treg cell expansion and function in vivo and to create therapeutic Treg cell products in vitro. We report that TNF receptor 2 (TNFR2) is a unique costimulus for naïve, thymus-derived (t)Treg cells from human blood that promotes their differentiation into non-lymphoid tissue (NLT)-resident effector Treg cells, without Th-like polarization. In contrast, CD28 costimulation maintains a lymphoid tissue (LT)-resident Treg cell phenotype. We base this conclusion on transcriptome and proteome analysis of TNFR2- and CD28-costimulated CD4+ Treg cells and conventional T (Tconv) cells, followed by bioinformatic comparison with published transcriptomic Treg cell signatures from NLT and LT in health and disease, including autoimmunity and cancer. These analyses illuminate that TNFR2 costimulation promotes Treg cell capacity for survival, migration, immunosuppression and tissue regeneration. Functional studies confirmed improved migratory ability of TNFR2-costimulated tTreg cells. Flow cytometry validated the presence of the TNFR2-driven Treg cell signature in effector/memory Treg cells from the human placenta as opposed to blood. Thus, TNFR2 can be exploited as driver of NLT-resident Treg cell differentiation for adoptive cell therapy or antibody-based immunomodulation in human disease.
2024-01-24 | PXD048248 | Pride
Project description:Human Treg IFNg/IL-10 subpopulations
| PRJNA478058 | ENA
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. Genome-wide analysis of histone H3 K4 and K27 trimethylation in expanded human FOXP3+ Treg cells and FOXP3-losing Treg cells
2013-05-31 | E-GEOD-47510 | biostudies-arrayexpress
Project description:Here, we describe the development and application of a new oligonucleotide microarray to analyze human TReg cells. Using whole genome transcription data from human and mouse TReg cells we have compiled a unique microarray consisting of 350 TReg specific genes (Human TReg Chip). Highly purified CD4+CD25+ and CD4+CD25- T cells were isolated from peripheral blood of 11 healthy volunteers and used for expression profiling to highlight the impact of molecular changes. Keywords: cell type comparison
2006-01-31 | GSE3882 | GEO
Project description:Regulatory T cells (Treg) contribute to the crucial immunological processes of self-tolerance and immune homeostasis. However, the mechanisms underlying Treg function and cell fate decisions to differentiate between Treg and conventional T cells (Tconv) remain to be fully elucidated, especially at the histone modification level. Covalent modifications of histones establish and maintain chromatin structure, and regulate gene transcription events by facilitating access to cis-elements by trans-acting factors during mammalian development and cellular differentiation. We aimed to investigate the role of the methylation form of histone modification as related to Treg function and phenotype. High-resolution maps of the genome-wide distribution of monomethylated histone H3 lysine 4, H3K4me1, and the trimethylated form H3K4me3 were generated for human activated conventional CD4+CD25+FOXP3- T cells (aTconv) and CD4+CD25+FOXP3+ regulatory T cells (Treg) by sequencing using the Solexa 1G Genetic Analyzer. We found 2115 H3K4me3 regions corresponding to proximal promoter regions; the genes associated with these regions in Treg cells included the crucial transcription factor forkhead box P3 (FOXP3) and the chemokine receptor CCR7. We also identified 41024 Treg cell type-specific H3K4me1 regions. The majority of the H3K4me1 regions differing between the Treg and aTconv cells were located at promoter-distal sites, some of which were selected and consolidated to further examine enhancer activity in in vitro reporter gene assays. The findings from our study provide a comprehensive genome-wide dataset of lineage-specific H3K4me1 and H3K4me3 patterns in Treg and aTconv cells, which may control the differentiation decision, lineage commitment and cell type-specific gene regulation. This basic principle is likely not confined to the two closely-related T cell populations, but may apply generally to somatic cell lineages in adult organisms. Genome-wide distribution of monomethylated histone H3 lysine 4, H3K4me1, and the trimethylated form H3K4me3 in human activated conventional CD4+CD25+FOXP3- T cells (aTconv) and CD4+CD25+FOXP3+ regulatory T cells (Treg) (5 samples in total)
2011-01-31 | E-GEOD-26427 | biostudies-arrayexpress
Project description:The inflammasome initiates innate defense and inflammatory response by activating caspase-1 and pyroptotic cell death in myeloid cells1,2. It is comprised of an innate immune receptor/effector, pro-caspase-1 and a common adaptor molecule, ASC (apoptotic speck-containing protein with a CARD). Consistent with their pro-inflammatory function, inflammasome components including caspase-1, ASC and NLRP3, are known to exacerbate autoimmunity during experimental autoimmune encephalomyelitis (EAE) by enhancing IL-1 and IL-18 secretion in myeloid cells3-6. Here we show an unexpected function of a DNA-binding inflammasome effector, AIM2 (Absent in Melanoma 2)7-10, in restraining autoimmunity by performing EAE in both whole body and Treg-specific deletion of Aim2–/– mice. AIM2 is highly expressed by human and mouse Treg cells and it is essential to attenuate EAE. RNA-seq, biochemical and metabolic analyses revealed that AIM2 attenuates mTOR, Myc and immune-metabolic functions in both Treg cells isolated in vivo and Treg cells induced in vitro with TGF-. Importantly, we found AIM2 physically interacted with RACK1 in Treg cells to facility the PP2A/RACK1/Akt-mTOR signaling, which is identified as a central component downstream of AIM2 that controls Treg cell function and stability. While AIM2 is generally accepted as an inflammasome effector in myeloid cells, this report reveals a previously unappreciated T cell-intrinsic role of AIM2 in maintaining Treg cell function to restrain autoimmunity. This is achieved by diminishing Akt-mTOR signaling to regulate Treg stability under inflammation, and altering immune-metabolism in Treg cells.
2021-01-27 | PXD018638 | Pride
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:In this screen we compared cDNA from rTreg (AICD resistent TReg cells) against cDNA derived from all CD4+CD25hi Treg for further molecular characterization of rTreg Experiment Overall Design: Single comparison of rTReg vs. TReg. We pooled rTreg-cDNA derived from FACS-sorted CD4+CD25hi Treg of eight healthy blood donors and performed gene chip microarray analysis.
2008-06-12 | E-GEOD-4243 | biostudies-arrayexpress