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Junctional Epithelial Plakoglobin facilitates intestinal inflammation by p38MAPK-Dependent Activation of the Inflammasome

GSE280558 Mus musculus (mouse) Single-cell RNA-seq 15 samples Submitted 2025/08/19 Platform GPL30172
At a glance

Single-cell RNA-seq · mouse · 15 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
15 samples: 6 × organoid JUPfl/fl vs 3 × organoid iVilCre ERT2JUPfl/fl vs 3 × iVilCre ERT2JUPfl/fl vs 3 × DSS colitis JUPfl/flGroups 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
Junctional epithelial Plakoglobin facilitates intestinal inflammation by p38MAPK-dependent activation of the inflammasomeMucosal immunology · 2025
Summary (written by the submitters)
Background and Aims: Desmosomes play an underexplored role in intestinal epithelial homeostasis and have been linked to the pathogenesis of inflammatory bowel diseases. Here, we assessed a novel function of the desmosomal plaque protein plakoglobin (JUP) in initiating the innate immune response that facilitates intestinal inflammation.
Read the full summary ↓
Methods: Surgical tissue samples of patients with Crohn’s Disease (CD) were collected and characterized for junctional protein changes. Mouse models using an intestinal epithelial-specific and inducible VilCreERT2-mediated conditional knockout of Jup under basal conditions and in acute dextran-sodium sulfate (DSS)-induced colitis were characterized using functional analyses, single cell and bulk sequencing. Intestinal organoids served to determine molecular mechanisms. Results: In patients with CD and in murine DSS colitis, loss of JUP was evident. Intestinal epithelial-specific knockout of Jup in mice resulted in augmented submucosal infiltration of macrophages and neutrophils and in an overall activation of the inflammasome. However, loss of intestinal barrier function, bacterial translocation or altered microbial composition were absent under basal conditions. In DSS-induced colitis, epithelial Jup-deficiency led to increased disease activity and strong activation of interleukin IL23/17-signalling compared to littermate controls with neutrophils representing the major source of IL23 under these conditions. Mechanistically, intestinal epithelial organoids lacking Jup demonstrated robust NLRP1 inflammasome activation due to p38MAPK hyperphosphorylation. This activation was evidenced by increased expression of NLRP1, IL1β, and IL18 in Jup-deficient intestinal epithelial cells, which was mitigated by p38MAPK inhibition. Conclusion: These findings point to a novel role for JUP in initiating intestinal inflammation. The loss of JUP in tissues from CD patients underscores its potential relevance in disease pathology.
Published in
Junctional epithelial Plakoglobin facilitates intestinal inflammation by p38MAPK-dependent activation of the inflammasome
Kelm M, Burkard N, Hörner M et al. · Mucosal immunology 2025 · PMID 40816453 · doi:10.1016/j.mucimm.2025.08.003
This dataset
Open GSE280558 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 GSE280558_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 PRJNA1179407 and SRA study SRP541791. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40816453) ↗
Study design
6 × organoid JUPfl/fl vs 3 × organoid iVilCre ERT2JUPfl/fl vs 3 × iVilCre ERT2JUPfl/fl vs 3 × DSS colitis JUPfl/fl

Supports a between-group comparison across 15 samples.

How we read this: 4 replicated groups read from 15 sample titles; they account for 15 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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