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A20’s Linear Ubiquitin Binding Motif Restrains Pathogenic Activation of TH17/22 cells and IL-22 Driven Enteritis [RNA-Seq]

GSE296201 Mus musculus (mouse) RNA-seq (gene expression) 18 samples Submitted 2025/06/12 Platform GPL34290
At a glance

RNA-seq (gene expression) · mouse · 18 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
18 samples: 6 × mProxSmallIntestine_A20ZF7 vs 5 × mProxSmallIntestine_WT vs 4 × mProxSmallIntestine_A20ZF7_Il22KO vs 3 × mProxSmallIntestine_Il22KOGroups 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
A20's linear ubiquitin-binding motif restrains pathogenic activation of Th17 cells and IL-22-driven enteritisThe Journal of clinical investigation · 2025
Summary (written by the submitters)
A20, encoded by the TNFAIP3 gene, is a protein linked to Crohn and celiac disease in humans. We show that mice expressing point mutations in A20’s M1-ubiquitin binding zinc-finger 7 (ZF7) domain spontaneously develop proximal enteritis that requires both luminal microbes and T cells. Cellular and transcriptomic profiling reveal expansion of TH17/22 cells and exuberant expression of IL-17A and IL-22 in intestinal lamina propria of A20ZF7 mice.
Read the full summary ↓
While deletion of IL-17A from A20ZF7 mice exacerbates enteritis, deletion of IL-22 abrogates intestinal epithelial cell hyperproliferation, barrier dysfunction, and alarmin expression. Colonization of adult germ-free mice with normal luminal flora drives duodenal IL-22 expression and duodenitis. A20ZF7 TH17/22 cells autonomously express more RORgammat and IL-22 after differentiation in vitro. ATAC sequencing identified an enhancer region upstream of the Il22 gene, and this enhancer demonstrated increased activating histone acetylation coupled with exaggerated Il22 transcription in A20ZF7 T cells. Acute inhibition of RORgammat normalized histone acetylation at this enhancer. Finally, CRISPR/Cas9-mediated ablation of A20ZF7 in human T cells increases RORgammat expression and IL22 transcription. These studies link A20’s M1-ubiquitin binding function with RORgammat expression, expansion of TH17/22 cells, and epigenetic activation of IL-22 driven enteritis.
Published in
A20's linear ubiquitin-binding motif restrains pathogenic activation of Th17 cells and IL-22-driven enteritis
Bowman CJ, Stibor DM, Sun X et al. · The Journal of clinical investigation 2025 · PMID 40892518 · doi:10.1172/JCI187499
This dataset
Open GSE296201 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 GSE296201_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 PRJNA1258204 and SRA study SRP582899. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40892518) ↗
Study design
6 × mProxSmallIntestine_A20ZF7 vs 5 × mProxSmallIntestine_WT vs 4 × mProxSmallIntestine_A20ZF7_Il22KO vs 3 × mProxSmallIntestine_Il22KO

Supports a between-group comparison across 18 samples.

How we read this: 4 replicated groups read from 18 sample titles; they account for 18 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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