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Combined inhibition of IL-1, IL-33 and IL-36 signaling by targeting IL1RAP ameliorates skin and lung fibrosis in preclinical models of Systemic Sclerosis

GSE255031 Mus musculus (mouse) RNA-seq (gene expression) 21 samples Submitted 2024/04/30 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 21 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
Mus musculus (mouse)
Samples
21 samples: 5 conditions, mostly with about 4 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
Combined inhibition of IL-1, IL-33 and IL-36 signalling by targeting IL1RAP ameliorates skin and lung fibrosis in preclinical models of systemic sclerosisAnnals of the rheumatic diseases · 2024
Summary (written by the submitters)
Background: The IL-1 receptor accessory protein (IL1RAP) is an essential co-receptor required for signaling through the IL-1, IL-33 and IL-36 receptors. Here, we investigate the antifibrotic potential of the combined inhibition of these cytokines by an anti-IL1RAP antibody to provide a scientific background for clinical development in systemic sclerosis (SSc).
Read the full summary ↓
Methods: The expression of IL1RAP-associated signaling molecules was determined by data mining of publicly available RNAseq data as well as by imaging mass cytometry (IMC). Efficacy of therapeutic dosing of anti-IL1RAP antibodies was determined in three complimentary mouse models: chronic sclerodermatous graft-versus-host-disease (cGvHD), bleomycin-induced dermal fibrosis model and topoisomerase-I (topo)-induced fibrosis. Results: SSc skin showed upregulation of IL1RAP and IL1RAP-related signaling molecules on mRNA and protein level compared to normal skin. IL-1, IL-33, and IL-36 all regulate distinct genes sets related to different pathophysiological processes in SSc. The responses of human fibroblasts and endothelial cells to IL-1, IL-33, and IL-36 were completely blocked by treatment with an anti-IL1RAP-antibody in vitro. Moreover, anti-IL1RAP antibody treatment reduced dermal and pulmonary fibrosis in cGvHD-, bleomycin- and topoisomerase-induced fibrosis. Importantly, RNAseq analyses revealed effects of IL1RAP inhibition on multiple processes related to inflammation and fibrosis that are also deregulated in human SSc skin. Conclusion: This study provides first evidence for the therapeutic benefits of targeting of IL1RAP in SSc. Our findings have high translational potential as the anti-IL1RAP antibody CAN10 has recently entered a phase 1 clinical trial.
Published in
Combined inhibition of IL-1, IL-33 and IL-36 signalling by targeting IL1RAP ameliorates skin and lung fibrosis in preclinical models of systemic sclerosis
Grönberg C, Rattik S, Tran-Manh C et al. · Annals of the rheumatic diseases 2024 · PMID 38594058 · doi:10.1136/ard-2023-225158
This dataset
Open GSE255031 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 GSE255031_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: 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 PRJNA1073269 and SRA study SRP488069. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38594058) ↗
Study design
5 conditions, mostly with about 4 replicates each
Allogeneic treated Nintedanib ×5 Syngenic ×4 Allogeneic treated isotype control ab ×4 Allogeneic treated ddH2O ×4 Allogeneic treated anti-IL1RAP ab ×4

Supports a between-group comparison across 21 samples.

How we read this: 5 replicated groups read from 21 sample titles; they account for 21 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
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