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Dimethyl Fumarate Restores Functional Vitamin-D3 Tolerogenic Dendritic Cells differentiated from Multiple Sclerosis Patients

GSE267576 Homo sapiens (human) RNA-seq (gene expression) 68 samples Submitted 2024/12/13 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 68 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Homo sapiens (human)
Samples
68 samples: 6 conditions, mostly with about 19 replicates eachGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper
Targeting aryl hydrocarbon receptor functionally restores tolerogenic dendritic cells derived from patients with multiple sclerosisThe Journal of clinical investigation · 2024
Summary (written by the submitters)
Multiple Sclerosis (MS) is a chronic disease characterised by dysregulated self-reactive immune responses damaging neurons’ myelin sheath, causing disability. The primary therapeutic option, immunosuppressants, inhibit pathogenic anti-myelin responses but depresses the entire immune system. Antigen-specific autologous tolerogenic dendritic cell (tolDC) therapies offer an approach to restore tolerance to auto-antigens without causing generalised immunosuppression.
Read the full summary ↓
However, immune dysregulation in MS could impact the phenotype and functionality of the starting material for cell therapy. In this study, we defined the immune signature of CD14+ monocytes, mature dendritic cells (mDCs) and Vitamin D3 tolDCs (VitD3-tolDCs) isolated from MS patients and healthy donors (HD). By using a multi-omic approach, we identified a shift in these cell types toward a proinflammatory profile dominated by alterations in the AhR pathway and increased NFkB signalling. Moreover, tolDCs isolated from MS patients showed reduced tolerogenic properties compared to those from HD, which were fully restored through AhR agonism and NFkB downregulation through in vivo or in vitro supplementation with Dimethyl Fumarate (DMF). Remarkably, a combined therapy of DMF and VitD3-tolDC was more efficient to reduce the clinical score of experimental autoimmune encephalomyelitis mice than monotherapies. In summary, we demonstrate that DMF restores the functionality of VitD3-tolDCs derived from MS patients. Moreover, a combined therapy with DMF and VitD3-tolDCs could offer enhanced therapeutic potential in treating MS.
Published in
Targeting aryl hydrocarbon receptor functionally restores tolerogenic dendritic cells derived from patients with multiple sclerosis
Fondelli F, Willemyns J, Domenech-Garcia R et al. · The Journal of clinical investigation 2024 · PMID 39287981 · doi:10.1172/JCI178949
This dataset
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE267576_RAW.tar (it can run to tens of gigabytes).

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1111870 and SRA study SRP507953. Searching any of these in the dataset finder brings you back here.

Study design
6 conditions, mostly with about 19 replicates each
Monocytes from healthy dono ×19 Monocytes from MS patient ×19 tolDCs from MS patient ×10 mDCs from MS patient ×9 tolDCs from healthy dono ×6 mDCs from healthy dono ×5

Supports a case/control comparison: 38 samples read as cases, 30 as controls.

How we read this: 6 replicated groups read from 68 sample titles; they account for 68 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

+ 28 more — browse all 68 samples with per-sample file links →

Datasets on a similar topic

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