GEO series

Interferon subverts an AHR-JUN axis to promote CXCL13+ T cells in lupus [AHR]

GSE233045 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 12 samples Submitted 2024/07/08 Platform GPL16791

At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 12 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: 12 samples: 3 × CD4_mem_sgNT_AHR_CnR vs 3 × CD4_mem_sgAHR_AHR_CnR vs 3 × CD4_mem_sgNT_IgG_CnR vs 3 × CD4_mem_sgAHR_IgG_CnRGroups 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: Interferon subverts an AHR-JUN axis to promote CXCL13(+) T cells in lupusNature · 2024

Summary (written by the submitters)

SLE is prototypical autoimmune disease driven by pathologic T cell-B cell interactions. Expansion of B cell-helper T cells including T follicular helper (Tfh) and T peripheral helper (Tph) cells is a prominent feature of systemic lupus erythematosus (SLE). Human Tfh and Tph cells characteristically produce high levels of the B cell chemoattractant CXCL135,6, yet regulation of T cell CXCL13 production and the relationship between CXCL13+ T cells and other T cell states remains unclear.

Read the full summary ↓

Here, we identify an imbalance in CD4 T cell phenotypes in SLE patients, with expansion of PD-1+/ICOS+ CXCL13+ T cells and reduction of CD96hi IL-22+ T cells. Using CRISPR screens, we identify the aryl hydrocarbon receptor (AHR) as a potent negative regulator of CXCL13 production by human CD4 T cells. Transcriptomic, epigenetic, and functional studies demonstrate that AHR coordinates with AP-1 family member JUN to prevent CXCL13+ Tph/Tfh cell differentiation and promote an IL-22+ phenotype. Type I interferon (IFN), a pathogenic driver of SLE7, opposes AHR and JUN to promote T cell production of CXCL13. These results place CXCL13+ Tph/Tfh cells on a polarization axis opposite from Th22 cells and reveal AHR, JUN, and IFN as key regulators of these divergent T cell states.

Published in

Interferon subverts an AHR-JUN axis to promote CXCL13(+) T cells in lupus

Law C, Wacleche VS, Cao Y et al. · Nature 2024 · PMID 38987586 · doi:10.1038/s41586-024-07627-2

This dataset

Open GSE233045 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 GSE233045_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 PRJNA974832 and SRA study SRP438820. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38987586) ↗

Study design

3 × CD4_mem_sgNT_AHR_CnR vs 3 × CD4_mem_sgAHR_AHR_CnR vs 3 × CD4_mem_sgNT_IgG_CnR vs 3 × CD4_mem_sgAHR_IgG_CnR

Supports a between-group comparison across 12 samples.

How we read this: 4 replicated groups read from 12 sample titles; they account for 12 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

GSM7400844 CD4_mem_sgNT_AHR_CnR_Rep1 CD4_mem_sgNT_AHR_CnR
GSM7400845 CD4_mem_sgNT_AHR_CnR_Rep2 CD4_mem_sgNT_AHR_CnR
GSM7400846 CD4_mem_sgAHR_AHR_CnR_Rep1 CD4_mem_sgAHR_AHR_CnR
GSM7400847 CD4_mem_sgAHR_AHR_CnR_Rep2 CD4_mem_sgAHR_AHR_CnR
GSM7400848 CD4_mem_sgNT_IgG_CnR_Rep1 CD4_mem_sgNT_IgG_CnR
GSM7400849 CD4_mem_sgNT_IgG_CnR_Rep2 CD4_mem_sgNT_IgG_CnR
GSM7400850 CD4_mem_sgAHR_IgG_CnR_Rep1 CD4_mem_sgAHR_IgG_CnR
GSM7400851 CD4_mem_sgAHR_IgG_CnR_Rep2 CD4_mem_sgAHR_IgG_CnR
GSM8009227 CD4_mem_sgNT_AHR_CnR_Rep3 CD4_mem_sgNT_AHR_CnR
GSM8009228 CD4_mem_sgAHR_AHR_CnR_Rep3 CD4_mem_sgAHR_AHR_CnR
GSM8009229 CD4_mem_sgNT_IgG_CnR_Rep3 CD4_mem_sgNT_IgG_CnR
GSM8009230 CD4_mem_sgAHR_IgG_CnR_Rep3 CD4_mem_sgAHR_IgG_CnR

Datasets on a similar topic

GSE233050 Interferon subverts an AHR-JUN axis to promote CXCL13+ T cells in lupus 76 samples shares ahr-jun, cxcl13, ahr, interferon, subverts, promote, lupus, axis
GSE252917 Interferon subverts an AHR-JUN axis to promote CXCL13+ T cells in lupus [JUN IFN] 12 samples shares ahr-jun, cxcl13, ahr, interferon, subverts, promote, lupus, axis
GSE277730 Interferon subverts an AHR-JUN axis to promote CXCL13+ T cell in lupus [Time_coure_RNAseq] 24 samples shares ahr-jun, cxcl13, ahr, interferon, subverts, promote, lupus, axis
GSE302359 Interferons promote autophagy via the STAT1/STAT5B-SOCS1 axis 12 samples shares interferon, promote, axis
GSE240497 Activation of a nongenetic AHR-ELMSAN1 axis optimizes BET-targeting therapy and suppresses leukemia stem cells in preclinical models 66 samples shares ahr, axis
GSE240496 Activation of a nongenetic AHR-ELMSAN1 axis optimizes BET-targeting therapy and suppresses leukemia stem cells in preclinical models [RNA-Seq] 24 samples shares ahr, axis
GSE277909 Epigenetic attenuation of interferon signaling drives aging-related improvements in systemic lupus 271 samples shares interferon, lupus
GSE299256 Positionally distinct interferon-stimulated dermal immune-acting fibroblasts promote neutrophil recruitment in Sweet's syndrome. 116 samples shares interferon, promote

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