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Caspase-8 silences cell death-independent constitutive immune activation driven by tonic TNF-α

GSE288233 Mus musculus (mouse) RNA-seq (gene expression) 16 samples Submitted 2026/03/19 Platform GPL30172
At a glance

RNA-seq (gene expression) · mouse · 16 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
16 samples: 4 × M-CSF M + vehicle vs 4 × M-CSF M + z-IETD-fmk vs 4 × BM-derived neutrophils + vehicle vs 4 × BM-derived neutrophils + z-IETD-fmkGroups 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
Caspase-8 silences cell death-independent constitutive immune activation driven by tonic TNF-αEMBO reports · 2026
Summary (written by the submitters)
Caspase-8 maintains organismal integrity by preventing cell death and secondary inflammation in selected epithelial and endothelial tissues. Here we show that caspase-8 also controls a systemic, cell death-independent inflammatory pathway that is constitutively activated during homeostasis. In vivo, selective caspase-8 inhibition produces, in the absence of other stimuli, marked neutrophilia driven by circulating proinflammatory and chemotactic cytokines.
Read the full summary ↓
In vitro, caspase-8 inhibition triggers in neutrophils, but not in macrophages, a profound transcriptional response associated with the release of IL-1βand other cytokines. This process requires tonic TNF-α production by neutrophils, which acts autocrinally to sequentially activate RIPK1, RIPK3,MAPKs and NF-κB. The IL-1βrelease induced by caspase-8 inhibition requires gasdermin D and neutrophil serine proteases, but not canonical inflammasome components, such as NLRP3 and ASC, or gasdermin E. Our data unveil the mechanistic features of a neutrophil-centric, pro-inflammatory pathway that can be therapeutically targeted to augment host defenses against pathogenic agents.
Published in
Caspase-8 silences cell death-independent constitutive immune activation driven by tonic TNF-α
Lentini G, Coppolino F, Famà A et al. · EMBO reports 2026 · PMID 42260177 · doi:10.1038/s44319-026-00813-5
This dataset
Open GSE288233 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 GSE288233_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 PRJNA1214786 and SRA study SRP559421. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 42260177) ↗
Study design
4 × M-CSF M + vehicle vs 4 × M-CSF M + z-IETD-fmk vs 4 × BM-derived neutrophils + vehicle vs 4 × BM-derived neutrophils + z-IETD-fmk

Supports a between-group comparison across 16 samples.

How we read this: 4 replicated groups read from 16 sample titles; they account for 16 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
Datasets on a similar topic

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