GEO series

Calcineurin inhibition rescues alloantigen-specific central memory T cell subsets and promotes chronic GVHD

GSE255545 Mus musculus (mouse) Single-cell RNA-seq 3 samples Submitted 2024/04/30 Platform GPL30172

At a glance

Single-cell RNA-seq · mouse · 3 samples

What it is: Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart. Read from the summary: GEO's own type field only says 'expression profiling by sequencing', so confirm it in the paper.
Organism: Mus musculus (mouse)
Samples: 3 samples
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: Calcineurin inhibition rescues alloantigen-specific central memory T cell subsets that promote chronic GVHDThe Journal of clinical investigation · 2024

Summary (written by the submitters)

Calcineurin inhibitors (CNIs) constitute the backbone of modern acute graft-versus-host disease (aGVHD) prophylaxis regimens but have limited efficacy in the prevention and treatment of chronic GVHD (cGVHD). We investigated the effect of CNIs on immune tolerance after stem cell transplantation with discovery-based single cell gene expression and T-cell receptor (TCR) assays of clonal immunity in tandem with traditional protein-based approaches and preclinical modeling.

Read the full summary ↓

While CNIs suppress the clonal expansion in CD8+ T-cells, alloreactive CD4+ T-cell clusters preferentially expanded during GVHD. Moreover, CNIs mediated reversible dose-dependent suppression of T cell activation and all stages of donor T-cell exhaustion but favored the differentiation to central memory T-cells. Critically, CNIs promoted the expansion of both polyclonal and TCR-specific alloreactive central memory CD4+ T-cells with high self-renewal capacity that mediated cGVHD following drug withdrawal. In contrast to post-transplant cyclophosphamide (PT-Cy), CSA was ineffective in eliminating IL-17A-secreting alloreactive T cell clones that mediate cGVHD. Collectively, we show that although CNIs attenuate aGVHD, they paradoxically rescue alloantigen-specific central memory T-cells, especially within the CD4+ compartment in lymphoid and GVHD target tissues, thus predisposing to cGVHD. These data provide further evidence to caution against CNI-based immune suppression without concurrent approaches that eliminate alloreactive T-cell clones.

Published in

Calcineurin inhibition rescues alloantigen-specific central memory T cell subsets that promote chronic GVHD

Wang Y, Ullah MA, Waltner OG et al. · The Journal of clinical investigation 2024 · PMID 38828727 · doi:10.1172/JCI170125

This dataset

Open GSE255545 in finder → Find more mouse RNA-seq datasets →

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.

Series matrix ↓

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 GSE255545_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

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.

Raw reads on ENA ↗

What the files usually look like: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA1075330 and SRA study SRP489252. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38828727) ↗

Samples in this study

The sample list for this study is not cached yet. Press Load samples and it will be fetched from NCBI.

+ 3 more — browse all 3 samples with per-sample file links →

Datasets on a similar topic

GSE284107 Combination therapies of porcupine inhibition with ruxolitinib, ibrutinib or belumosudil in murine sclerodermatous GvHD 15 samples shares gvhd, inhibition
GSE306012 Temporal inhibition of ADAM17 in fibroblasts reduces stiffness and promotes vascularization following myocardial infarction 28 samples shares inhibition, promotes
GSE337703 p300/CBP inhibition promotes apoptosis in mouse embryos by impairing H1K75ac-mediated DNA repair from the 4-cell to blastocyst stage 8 samples shares inhibition, promotes
GSE306861 ALDH2 inhibition reprograms tubular epithelial cell metabolism and promotes renal injury susceptibility 8 samples shares inhibition, promotes
GSE326240 Prophylactic inhibition of LATS1/2 prior to high-dose irradiation promotes the regeneration of the damaged intestinal epithelium through Yap-dependent and independent mechanisms 8 samples shares inhibition, promotes
GSE318028 Pharmacological inhibition of FKBP51 mitigates early life adversity-induced social deficits 246 samples shares inhibition
GSE293819 Monitoring systemic immune responses to checkpoint inhibition in breast cancer reveals host responses and mechanisms of resistance 142 samples shares inhibition
GSE307181 Sex specific correction of maternal inflammation-induced behavioral abnormalities by the inhibition of colony-stimulating factor 1 receptor 96 samples shares inhibition

Search all mouse RNA-seq datasets in GEO →

Share this dataset

Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.