Cell-Type-Specific Transcriptome of CD4+, CD8+ T cells and CD14+ monocytes in multiple sclerosis
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ABSTRACT:
PROVIDER: PRJNA564629 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10089300_1.fastq.gz | Fastqsanger.gz | |||
| SRR10089300_2.fastq.gz | Fastqsanger.gz | |||
| SRR10089400_1.fastq.gz | Fastqsanger.gz | |||
| SRR10089400_2.fastq.gz | Fastqsanger.gz | |||
| SRR10089500_1.fastq.gz | Fastqsanger.gz |
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Project description:Multiple sclerosis (MS) is a chronic autoimmune and degenerative disease of the central nervous system, which develops in genetically predisposed individuals upon exposure to environmental influences. Environmental triggers of MS, such as viral infections or smoking, were demonstrated to affect DNA methylation, and thus to involve this important epigenetic mechanism in the development of pathological processes. To identify DNA methylation hallmarks, associated with MS, we performed genome-wide DNA methylation profiling of two cell populations (CD4+ T-lymphocytes and CD14+ monocytes), collected from the same individuals (relapsing-remitting MS patients and healthy subjects), using Illumina 450K methylation arrays. We revealed significant changes in DNA methylation for both cell populations of studied groups. In CD4+ cells the majority of differentially methylated positions (DMPs) were shown to be hypomethylated, while in CD14+ cells – hypermethylated in MS patients. Noteworthy, in CD4+, but not in CD14+ cells, we found differential methylation of HLA-DRB6 gene from HLA locus, which is known to have the strongest genetic association with MS. Besides, about 20% of DMPs identified in studied cells were identical; they all had the same direction of methylation changes in both cell populations and may be involved in basic epigenetic processes occuring in MS. These findings suggest that the epigenetic mechanism of DNA methylation in immune cells contributes to MS; further studies are now required to validate these results and understand their functional significance.
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2020-11-05 | E-MTAB-8982 | biostudies-arrayexpress
Project description:Multiple sclerosis (MS) is a chronic autoimmune and degenerative disease of the central nervous system, which develops in genetically predisposed individuals upon exposure to environmental influences. Environmental triggers of MS, such as viral infections or smoking, were demonstrated to affect DNA methylation, and thus to involve this important epigenetic mechanism in the development of pathological processes. To identify DNA methylation hallmarks, associated with MS, we performed genome-wide DNA methylation profiling of two cell populations (CD4+ T-lymphocytes and CD14+ monocytes), collected from the same individuals (relapsing-remitting MS patients and healthy subjects), using Illumina 450K methylation arrays. We revealed significant changes in DNA methylation for both cell populations of studied groups. In CD4+ cells the majority of differentially methylated positions (DMPs) were shown to be hypomethylated, while in CD14+ cells – hypermethylated in MS patients. Noteworthy, in CD4+, but not in CD14+ cells, we found differential methylation of HLA-DRB6 gene from HLA locus, which is known to have the strongest genetic association with MS. Besides, about 20% of DMPs identified in studied cells were identical; they all had the same direction of methylation changes in both cell populations and may be involved in basic epigenetic processes occuring in MS. These findings suggest that the epigenetic mechanism of DNA methylation in immune cells contributes to MS; further studies are now required to validate these results and understand their functional significance.
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2012-07-25 | E-GEOD-39643 | biostudies-arrayexpress
Project description:Genome-wide DNA methylation profiling identifies epigenetic changes in CD4+ and CD14+ cells of multiple sclerosis patients [CD14]
| PRJNA782259 | ENA
Project description:We investigated the innate immune system in the SOD1 ALS model. We found that splenic Ly6CHi monocytes were activated and their progressive recruitment to the spinal cord, but not brain, correlated with neuronal loss. We found a decrease in resident microglia in the spinal cord with disease progression. Two months prior to disease onset, splenic Ly6CHi monocytes had an M1 signature which included increased CCR2. At one month prior to disease onset, microglia expressed increased CCL2 and other chemotaxis-associated molecules. Microglia derived from the spinal cord of SOD1 mice recruited Ly6C+ monocytes to the CNS. Treatment with anti-Ly6C mAb modulated the Ly6CHi monocyte cytokine profile, reduced monocyte recruitment to the spinal cord, diminished neuronal loss and extended survival. In humans with ALS, CD14+/CD16- monocytes (analogue of Ly6CHi monocytes) exhibited an ALS specific microRNA inflammatory signature similar to that observed in the SOD1 mouse providing a direct link between the animal model and the human disease. Thus, the SOD1-like profile of monocytes in ALS subjects may serve as a biomarker for disease stage or progression. Our results suggest that recruitment of inflammatory monocytes plays an important role in disease progression and that modulation of these cells is a potential therapeutic approach. This study used the NanoString nCounter hybridization system and nCounter miRNA expression assays to identify and quantitate miRNAs in blood CD14+CD16- monocytes from ALS, MS and HC subjects
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Project description:Treatment of multiple sclerosis (MS) patients with sphingosine-1-phosphate receptor agonist fingolimod (FTY) increases for unknown reasons the risk for symptomatic reactivation of alpha-herpesviruses, in particular of varicella zoster virus (VZV), but not of other co-infecting herpesviruses (e.g. human cytomegalovirus (HCMV). To elucidate this specific signal in adverse events, we systematically assessed changes in global and herpesvirus-specific immune responses and signatures in MS patients before and during FTY therapy. In addition to phenotypical and functional changes, we thought to identify FTY-induced modifications on the gene expression level, which might add to perturbations in antiviral immune responses. Therefore, gene expression of CD4+ EM T cells and CD14+ monocytes were analyzed. These two subsets, CD4+ EM T cells and CD14+ monocytes, were isolated from PBMC of six female RRMS patients collected before (V0) and after 9 months of FTY therapy (V9) for RNA sequencing (RNASeq). Comparison of gene expression profiles of monocytes between V0 and V9 revealed 226 down- and 38 upregulated genes. Gene ontology categories and pathway analysis detected most significant alterations for genes involved in immune response, defense against viruses as well as type-1 interferon signaling pathways. Next, we compared gene expression profiles of CD4+ EM T cells collected at V0 and V9 of FTY therapy and found 314 down- and 219 upregulated genes. The most significantly modified pathways were involved in immune responses, including NK cell chemotaxis, cytotoxicity and antiviral responses. In summary, gene expression analysis of monocytes suggests that HCMV might be more susceptible to reactivation during FTY treatment because of FTY-induced modifications of immune control pathways important for HCMV latency. However, increased cytolytic potential of CD4+ EM T cells and expansion of HCMV-specific CD4+ T cells might counteract synthesis or release of viral particles and prevent viremia.
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Project description:Genome-wide DNA methylation profiling identifies epigenetic changes in CD4+ and CD14+ cells of multiple sclerosis patients [CD4]
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