GEO series

Opposing Regulation of TNF Responses and IL-1b+ Macrophages by PGE2-cAMP Signaling and IFN-g [ATAC-seq]

GSE272017 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 24 samples Submitted 2025/03/27 Platform GPL24676

At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 24 samples

What it is: ChIP-seq / ATAC-seq (genome binding and open chromatin)Where proteins bind the genome, or which regions are open and active.
Organism: Homo sapiens (human)
Samples: 24 samples: 8 conditions, mostly in triplicateGroups 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: Opposing regulation of TNF responses by IFN-γ and a PGE2-cAMP axis that is apparent in rheumatoid and immune checkpoint inhibitor-induced arthritis human IL-1β+ macrophageseLife · 2025

Summary (written by the submitters)

IL-1b-expressing macrophages elicited by cooperation between PGE2 and TNF signaling have been identified and proposed to be pathogenic in rheumatoid arthritis (RA) and pancreatic cancer, but mechanisms that induce these cells and the extent to which they contribute to arthritic phenotypes are not known. In this study we used an integrated transcriptomic and epigenomic analysis in primary human monocytes to study PGE2-TNF crosstalk, and how it is regulated by IFN-g, as occurs in RA synovial macrophages.

Read the full summary ↓

We identified a (TNF + PGE2)-induced gene expression signature that is enriched in RA and post-immune checkpoint blockade arthritis macrophage subsets and includes genes in pathogenic IL-1, Notch and neutrophil chemokine pathways. This gene expression signature, which is distinct from canonical inflammatory NF-kB target genes such as TNF, IL6 and IL12B, was driven by cooperation of PGE2-induced AP-1, CEBP and NR4A family transcription factors with TNF-induced NF-kB activity. Unexpectedly, IFN-g suppressed induction AP-1, CEBP and NR4A activity to ablate induction of IL-1, Notch and neutrophil chemokine genes, while promoting expression of distinct inflammatory genes such as TNF and T cell chemokines like CXCL10. These results reveal the basis for synergistic induction of inflammatory genes by PGE2 and TNF, and a novel regulatory axis whereby IFN-g and PGE2 oppose each other to determine the balance between two distinct TNF-induced inflammatory gene expression programs.

Published in

Opposing regulation of TNF responses by IFN-γ and a PGE2-cAMP axis that is apparent in rheumatoid and immune checkpoint inhibitor-induced arthritis human IL-1β+ macrophages

Sokhi UK, Yuan R, Mishra B et al. · eLife 2025 · PMID 40662950 · doi:10.7554/eLife.104367

This dataset

Open GSE272017 in finder → Find more human ChIP / ATAC / CUT&Tag 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 GSE272017_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: Look for peak files (.bed, .narrowPeak) and signal tracks (.bigWig) among the supplementary files; the raw reads are on ENA.

Also filed as BioProject PRJNA1134641 and SRA study SRP519299. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40662950) ↗

Study design

8 conditions, mostly in triplicate

C3 ×3 IFNg_C3 ×3 IFNg_P3 ×3 IFNg_T3 ×3 IFNg_TP3 ×3 P3 ×3 T3 ×3 TP3 ×3

Supports a between-group comparison across 24 samples.

How we read this: 8 replicated groups read from 24 sample titles; they account for 24 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

GSM8391002 C3_Rep1 C3
GSM8391003 C3_Rep2 C3
GSM8391004 C3_Rep3 C3
GSM8391005 IFNg_C3_Rep1 IFNg_C3
GSM8391006 IFNg_C3_Rep2 IFNg_C3
GSM8391007 IFNg_C3_Rep3 IFNg_C3
GSM8391008 IFNg_P3_Rep1 IFNg_P3
GSM8391009 IFNg_P3_Rep2 IFNg_P3
GSM8391010 IFNg_P3_Rep3 IFNg_P3
GSM8391011 IFNg_T3_Rep1 IFNg_T3
GSM8391012 IFNg_T3_Rep2 IFNg_T3
GSM8391013 IFNg_T3_Rep3 IFNg_T3
GSM8391014 IFNg_TP3_Rep1 IFNg_TP3
GSM8391015 IFNg_TP3_Rep2 IFNg_TP3
GSM8391016 IFNg_TP3_Rep3 IFNg_TP3
GSM8391017 P3_Rep1 P3
GSM8391018 P3_Rep2 P3
GSM8391019 P3_Rep3 P3
GSM8391020 T3_Rep1 T3
GSM8391021 T3_Rep2 T3
GSM8391022 T3_Rep3 T3
GSM8391023 TP3_Rep1 TP3
GSM8391024 TP3_Rep2 TP3
GSM8391025 TP3_Rep3 TP3

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