Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Heterogeneous CD3 expression levels in differing T-cell subsets account for in vivo anti-CD3-mediated immune resetting

ABSTRACT: The tolerogenic anti-CD3 monoclonal antibodies (anti-CD3) are promising compounds for the treatment of type 1 diabetes (T1D). Anti-CD3 administration induces transient T-cell depletion both in preclinical and in clinical studies. Notably, said depletion mainly affects CD4+ but not CD8+ T cells. Moreover, T1D reversal in preclinical models is accompanied by the selective expansion of CD4+FOXP3+ T regulatory (Treg) cells, which are fundamental for the long-term maintenance of anti-CD3-mediated tolerance. The mechanisms that lead to this immune-shaping by affecting mainly CD4+ T effector cells while sparing CD4+FOXP3+ Treg cells have still to be fully elucidated. This study shows that CD3 expression levels differ from one T-cell subset to another. CD4+FOXP3- T cells contain higher amounts of CD3 molecules than do CD4+FOXP3+ and CD8+ T cells both in mice and in humans. Said differences may explain the anti-CD3-mediated immune resetting that occurs in vivo after anti-CD3 administration in mice. In addition, transcriptome analysis demonstrates that CD4+FoxP3+ Treg cells are significantly less responsive than CD4+FoxP3- T cells to anti-CD3 treatment at molecular levels. Thus, heterogeneity in CD3 expression likely confers the various T-cell subsets differing susceptibility to in vivo tolerogenic anti-CD3-mediated modulation. This data sheds new light on the molecular mechanism that underlies anti-CD3-mediated immune resetting, and thus may open new opportunities to improve this promising treatment.

ORGANISM(S): FoxP3-GFP NOD mouse

SUBMITTER: Eliane Piaggio

PROVIDER: E-MTAB-2437 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Expression of the IL-17/Th17 axis in the development of acute renal allograft rejection

Project description:Genesets for the IL-17 pathway and Th17 T-helper cell subtype showed increasing enrichment in 33 pre-transplant donor biopsies and 33 matching post-transplant biopsies from patients with increasing Banff grades of acute rejection (no signficant abnormalities, n=17; borderline, n=4; ARIA, n=7; ARIB, n=6) in gene set analysis using SAM (GSA, FDR 0.5; 1000 permutations, log rank regression) for a total of 3307 publically available and manually curated gene-sets. 14 genes of the IL-17 pathway gene-set and 132 genes of the Th17 gene set segregated patients according to their histological diagnosis by unsupervised hierarchical clustering and principal component analysis. This study demonstrates a significant role for the IL-17 pathway in the development of acute renal allograft rejection. Therapeutically targeting the IL-17 pathway presents a promising option in transplantation medicine and can be acchieved through drug reposittioning. Keywords: IL-17 pathway, drug repositioning, gene set enrichment analysis A total of 66 human renal allograft protocol biopsies were included in this study, 33 biopsies obtained at implantation prior to revascularization and 33 protocol biopsies obtained after transplantation. Whole genome expression profiles were assessed using microarrays. This dataset is part of the TransQST collection.

2014-01-01 | E-GEOD-34437 | biostudies-arrayexpress

Transcriptome Shock Invokes Disruption of Parental Expression-Conserved Genes in Tetraploid Wheat

Project description:Allopolyploidy, entailing whole genome duplication (WGD) of merged divergent genomes of different species, often instigates transcriptome shock, whereby both total gene expression level and homeolog expression partitioning can be disrupted and remodeled. Little is known about the extent to which the parental expression-conserved genes will be disrupted/remodeled by allopolyploidization, nor the evolutionary relevancy of shock-induced expression repatterning. Here, by microarray-based gene expression profiling and gene-specific cDNA-pyrosequencing, we assessed transgenerational transcriptome shock in a synthetic allotetraploid wheat (AT2) with karyotype and basic morphology mimicking those of natural tetraploid wheat, Triticum turgidum. We show that the transcriptome shock in AT2 is exceptionally strong that it disrupted intrinsically conserved parental gene expression, and resulted in extensive expression nonadditivity in the newly formed allotetraploid plants. At total expression level, a substantial proportion of shock-induced novel expression, especially over-transgressive expression, was rapidly stabilized already in early generations of AT2. Extensive remodeling of homeolog expression occurred in AT2, including those genes that showed additive total expression, and which generated subgenome expression dominance, a pattern that mirrors T. turgidum. Thus, the shock-induced new patterns of gene expression at both the total expression level and subgenome homeolog partitioning showed evidence of evolutionary persistence. Complex relationships between homeolog expression remodeling and nonadditive total expression were observed in a tissue-specific manner. We have 9 samples including two tissues, leaf and young-inflorescence, respectively. Each sample has three replicates. So we overall have 54 samples.

2016-02-12 | E-GEOD-65844 | biostudies-arrayexpress

Local regulation and clinical impact of complement gene expression in deceased and living donor kidney allografts

Project description:The biopsy samples obtained at implantation segregated in 2 distinct groups according to donor origin, with a cluster of 319 unique identified genes higher expressed in DD compared to LD kidneys, and 329 genes lower expressed (false discovery rate <5%). Using pathway analysis software a significant local renal overrepresentation of complement genes in DD implantation biopsies was identified. Complement gene expression in DD kidneys related both to donor death and cold ischemia duration, and was associated with a slower onset of renal allograft function. In post-transplantation protocol biopsies, there was a continued overexpression of complement genes, regardless of donor source. The local renal complement gene expression variability in post-transplantation biopsies correlated with renal graft function. This study demonstrates a significant and clinically relevant local overexpression of complement genes in DD kidneys at engraftment and continuous functionally important regulation of complement gene expression after transplantation, regardless of donor source. Targeted therapy interfering with complement activation is an attractive therapeutic target that deserves further investigation in solid organ transplantation. Keywords: time course, genomics gene expression A total of 95 human renal allograft protocol biopsies were included in this study, 28 biopsies (14 DD, 14 LD) obtained at implantation prior to revascularization and 67 protocol biopsies obtained after transplantation. Whole genome expression profiles were assessed using microarrays. This dataset is part of the TransQST collection.

2008-04-16 | E-GEOD-11166 | biostudies-arrayexpress

OJeanJean_eRF3a_ATF4

Project description:We previously showed that eRF3a depletion in the human colon carcinoma cell line HCT116 p53+/+ induces mTOR signaling pathway inhibition (Chauvin et al., 2007) suggesting that eRF3a belongs to a regulatory mechanism that modulate mTOR activity. However, this mechanism and the precise role of eRF3a remain to be determined. Here, to elucidate the mechanism dictating mTOR signaling pathway inhibition, we aimed to define the transcript expression and polysome profiles of HCT116 cells after short interfering RNA (siRNA)-mediated depletion of eRF3a. Three days after HCT116 cells electroporation with either sh-3a1 which was previously shown for effectively silence eRF3a (Chauvin et al., 2005) or control shRNA (sh-Ctrl), total and polysome-associated RNAs were extracted and we conducted a microarray analysis of differentially expressed genes using the Illumina HumanHT-12 Expression BeadChips.

2012-08-30 | E-MEXP-3512 | biostudies-arrayexpress

Foie WTS vs WT

Project description:Transcriptional and polysomal analysis of mice liver hepatocytes after 4-hour refeeding as compared to overnight starved controls.

2013-01-24 | E-MEXP-3522 | biostudies-arrayexpress

Eliane_IL2.Rapa bis

Project description:Administration of low-dose IL-2 prevents and cures type 1 diabetes (T1D) in NOD mice by boosting pancreatic regulatory T cells (Tregs) and is currently being evaluated in humans. Here, to improve treatment efficacy we tested higher IL-2 doses that, despite further boosting Tregs, rapidly precipitated T1D in pre-diabetic mice due to generalized immune activation. Although the combination of rapamycin (RAPA) plus IL-2 prevents NOD T1D development, a recent clinical trial translating this strategy into patients was halted due to C-peptide decline. Here, we show that RAPA/IL-2 combination was also ineffective to cure new onset T1D in mice and, surprisingly, RAPA broke IL-2-induced tolerance in a reversible way. RAPA partially counteracted IL-2 effects on Tregs and the combined treatment unexpectedly, impaired glucose homeostasis at multiple levels, possibly explaining the clinical outcome. Our data help understand IL-2 alone or RAPA/IL-2 combination limitations and could lead to the design of improved T1D therapies.

2013-12-10 | E-MEXP-3789 | biostudies-arrayexpress

microRNA profiling by array of human skin melanoma and microenvironment

Project description:MicroRNAs are small non-coding molecules about 18-24 nucleotides long which can regulate expression of up to 60% of genes in a cell. So they are involved in many cellular processes. It has been demonstrated that miRNAs are involved in pathological processes, in particular in cancer and may be promising targets for differential diagnosis and therapy of cancer. This study is aimed at finding microRNAs involved in the development of melanoma, which could be potential targets for personalized treatment of this disease.

2019-01-01 | E-MTAB-7060 | biostudies-arrayexpress

siRNA profiling of human synovial fibroblasts depleted for clusterin

Project description:Analysis of synoviocytes cell form patients suffering of Rheumatoid arthritis and depleted for clusterin by siRNA knockdown. Note: this experiment was reloaded into ArrayExpress on 2nd December 2009 because the incorrect array design had originally been selected. The identifiers in the datafile were also fixed to match the array design.

2009-12-04 | E-TABM-653 | biostudies-arrayexpress

Comparison of lymph node negative (N0) and lymph node metastasis (N+) head and neck squamous-cell carcinomas (HNSCC)

Project description:A classifier was build on 82 training samples to differentiate between lymph node negative (N0) and lymph node metastasis (N+) head and neck squamous-cell carcinomas (HNSCC). The 102 predictor genes that resulted from this classifier where then validated against a independent validation set.

2005-01-09 | E-UMCU-11 | biostudies-arrayexpress

Transcription profiling of human brain tissue from an individual with neurological disease

Project description:Transcriptomic comparison of brain tissues

2010-11-25 | E-TABM-888 | biostudies-arrayexpress