Epigenome analysis of CD4 T cells from treated and untreated patients with multiple sclerosis (MS)
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ABSTRACT:
PROVIDER: PRJNA448427 | ENA |
REPOSITORIES: ENA
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Project description:Genome wide DNA methylation profiling of CD4 T cells from treated and untreated patients with multiple sclerosis. The Illumina InfiniumEPIC methylation Beadchip was used to obtain DNA methylation profiles across approximately 850,000 CpGs of CD4 T cells from patients with multiple sclerosis.
2018-04-03 | GSE112596 | GEO
Project description:The aim of this study was to identify differentially expressed genes in peripheral blood mononuclear cells from MS patients that were responders or non-responders to the neuroantigen myelin basic protein. Using microarray we measured mRNA-expression levels in freshly isolated peripheral blood mononuclear cells from 17 untreated patients with multiple sclerosis. Based on studies, measuring the responses of blood derived T-cells to myelin basic protein ex vivo, these 17 untreated MS-patients can be divided into two groups: 4 of the untreated multiple sclerosis patients had T-cells that responded to myelin basic protein ex vivo whereas 13 untreated MS patients had T-cells that did not respond to myelin basic protein ex vivo.
2014-11-28 | E-MTAB-2707 | biostudies-arrayexpress
Project description:Patient with multiple sclerosis improves during pregnancy while temporarily worsening post-partum. The reasons behind the disease modulation during pregnancy remain unknown. In this study, we have investigated the effect of pregnancy on circulating CD4+ and CD8+ T cells from patients with multiple sclerosis and healthy controls to gain a deeper understanding why patients with multiple sclerosis improves during pregnancy. We assessed epigenome-wide DNA methylation in CD4+ and CD8+ T cells obtained during (1st, 2nd and 3rd trimester) and after pregnancy (6 weeks post-partum), using the Infinium MethylationEPIC 850K array.
2023-09-23 | E-MTAB-12250 | biostudies-arrayexpress
Project description:Objective Hepatocyte growth factor (HGF) binds exclusively the c-Met surface receptor, and the HGF/c-Met axis regulates T-cell function in autoimmune diseases. We analyzed c-Met expression on human CD4 T cells in the blood and cerebrospinal fluid (CSF) from patients with multiple sclerosis (MS) versus non-inflammatory neurological disease (NIND), to better understand the role of CD4 T cells in MS. Methods We recruited 34 untreated MS patients (aged 28–43 years) and 10 NIND (aged 34–51 years) who underwent paired blood and CSF sampling at the time of diagnosis work-up. Phenotypic and functional CD4 T cells characterization was determined by flow cytometry and bulk RNA sequencing. Adhesion and transmigration capacities were studied to further characterize the function of c-Met+ CD4 T cells. Results c-Met+ memory CD4 T cells were detected at higher levels in both blood (median of 1.98%) and CSF (5.88%) in MS compared to NIND (0.37% and 0.68% respectively) (p<0.0001). Ex vivo c-Met+ CD4 T cells exhibited higher levels of GM-CSF, IL-17, IFN-γ and double positive IL-17+IFN-γ+ expression, compared with c-Met- CD4 T cells. c-Met+ CD4 T cells expressed increased levels of integrins – Itgα4β1 (VLA-4) and ItgαLβ2 (LFA-1) – compared with c-Met- CD4 T cells. Anti-Itgα4 (natalizumab) and anti-ItgαLβ2 (odulimomab) inhibited CD4 T cell transmigration with predominant inhibition of CD4 T cells expressing c-Met. Interpretation These results emphasize c-Met as an immune marker of highly pro-inflammatory and migratory CD4 T lymphocytes in both the periphery and central nervous system of MS patients.
2025-08-19 | GSE305678 | GEO
Project description:The human brain is populated by perivascular CD8+ and CD4+ T cells with a tissue-resident memory T (TRM)-cell phenotype. In multiple sclerosis (MS), these cells associate with white matter (WM) and, to a lesser extent, grey matter (GM) lesions. We here investigated the transcriptional and functional profile of brain-resident T cells. Of n=11 subsequent post-mortem brain donors, we isolated CD8+ and CD4+ effector memory and effector memory re-expressing CD45RA T cells from blood and CD8+ and CD4+ CD69+ T cells from corpus callosum WM and cortical GM. Additionally, brain CD69+ T cells were sorted from subcortical WM, corpus callosum WM, and medulla WM/GM of n=3–5 brain donors as well as from paired normal-appearing WM and GM and from WM and GM lesions of n=6 MS brain donors. In all donors, WM and GM T cells were overwhelmingly CD69+CD103+/-. Bulk RNA sequencing of CD8+ and CD4+ CD69+ T cells revealed TRM-cell signatures, as marked by differential expression of, among others, SELL (CD62L), ITGA1 (CD49a), and S1PR1. Notably, gene expression hardly differed between lesional and normal-appearing WM CD8+ and CD4+ CD69+ T cells in MS brains. Genes up-regulated in brain TRM cells were MS4A1 (CD20) and SPP1 (osteopontin, OPN). OPN is also abundantly expressed by microglia and has been shown to inhibit T-cell activity. In line with the increased presence of OPN in active MS lesions, we noticed a reduced production of the inflammatory cytokines IL-2, TNF, and IFNγ by MS lesion-derived CD8+ and CD4+ T cells ex vivo. This study discloses essential characteristics of human brain CD8+ and CD4+ TRM cells in non-MS and MS post-mortem WM and GM, reports OPN as a generic product of brain-resident immune cells, and shows a tight control of the activation state of TRM cells in MS lesions.
2022-12-05 | GSE216028 | GEO
Project description:<p>Monozygotic (MZ) twins have been widely employed for dissection of the relative contributions of genetics and environment in disease. In multiple sclerosis (MS), an autoimmune demyelinating disease that commonly causes neurodegeneration and disability in young adults, disease discordance in MZ twins has been interpreted to indicate environmental importance in pathogenesis. However, genetic and epigenetic differences between MZ twins have been described, challenging the accepted experimental paradigm in disambiguating effects of nature and nurture. Here, we report the genome sequences of one MS-discordant MZ twin pair and messenger RNA (mRNA) transcriptome and epigenome sequences of CD4+ lymphocytes from three MS-discordant, MZ twin pairs. No reproducible differences were detected between co-twins among ~3.6 million single nucleotide polymorphisms (SNPs) or ~0.2 million insertion-deletion polymorphisms (indels). Nor were any reproducible differences observed between siblings of the three twin pairs in HLA haplotypes, confirmed MS-susceptibility SNPs, copy number variations, mRNA and genomic SNP and indel genotypes, or expression of ~19,000 genes in CD4+ T cells. Only two to 176 differences in methylation of ~2 million CpG sites were detected between siblings of the three twin pairs, in contrast to ~800 differences in methylation between T cells of unrelated individuals and several thousand differences between tissues or normal and cancerous tissues. In the first systematic effort to estimate sequence variation among MZ co-twins, we did not find evidence for genetic, epigenetic or transcriptome differences that explained disease discordance. These are the first female, twin and autoimmune disease genome sequences reported.</p>
| phs000239 | dbGaP
Project description:Multiple sclerosis is the most common autoimmune disease of the central nervous system. Studying whole blood RNA from a cohort of 195 MS patients and 66 healthy controls, we identified gene expression signatures for interferon treatment and disease status by microarray analysis. Blood was collected at multiple time points (up to 3 for patients, 2 for controls). Patients were either untreated or treated with Interferon. In total, 626 Affymetrix exon arrays were analyzed, split into discovery and replication data sets. This metadata file contains information on all samples processed in the replication data set (n=102) when we compared gene expression in untreated MS patients (n=27) to healthy controls (n=25).
2013-06-17 | GSE41849 | GEO
Project description:Multiple sclerosis is the most common autoimmune disease of the central nervous system. Studying whole blood RNA from a cohort of 195 MS patients and 66 healthy controls, we identified gene expression signatures for interferon treatment and disease status by microarray analysis. Blood was collected at multiple time points (up to 3 for patients, 2 for controls). Patients were either untreated or treated with Interferon. In total, 626 Affymetrix exon arrays were analyzed, split into discovery and replication data sets. This metadata file contains information on all samples processed in the discovery data set (n=212) when we compared gene expression in untreated MS patients (n=62) to healthy controls (n=41).
2013-06-17 | GSE41848 | GEO
Project description:Upon antigen-specific T Cell Receptor (TCR) engagement, human CD4+ T cells proliferate and differentiate, a process associated with rapid transcriptional changes and metabolic reprogramming utilizing aerobic glycolysis together with maintenance of oxidative phosphorylation1,2. However, the role of glycolytic-reprogramming during T-cell activation remains largely unclear3,4,5. Here, we show that maintenance of cytosolic pyruvate production is an essential requirement for remodeling of the CD4+ T cell epigenome after TCR-engagement. Furthermore, we provide evidence that the local inflammatory environment sustains metabolic reprogramming of CD4+ T-cells and impacts histone modification in a pyruvate-dependent manner. Mechanistically, we demonstrate that rapid and sustained generation of cytosolic, but not mitochondrial, pyruvate is an essential step for acetyl-coA production and subsequent H3K27ac epigenome remodeling. TCR-activation was found to induce nuclear import of pyruvate dehydrogenase (PDH) and its association with both the p300 acetyltransferase and histone H3K27ac. Disrupting PDH nuclear import impacted expression of activation-induced genes. These results reveal a direct connection between CD4+ T cell metabolic reprogramming and transcriptional regulation, with the generation of cytosolic pyruvate being an essential step in T cell activation. These data support tight integration of metabolic enzymes and histone modifying enzymes, allowing metabolic reprogramming to fuel CD4+ T cell activation.
2023-10-27 | PXD018132 | Pride