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Impaired regulation by purinergic signaling axis contributes to CD8+ T cell dysregulation in STAT3 GOF

GSE311536 Homo sapiens (human) RNA-seq (gene expression) 24 samples Submitted 2026/07/23 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 24 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
Homo sapiens (human)
Samples
24 samples: 7 × scRNAseq STAT3GOF CD8+ T cells vs 7 × scTCRseq STAT3GOF CD8+ T cells vs 5 × scRNAseq healthy CD8+ T cells vs 5 × scTCRseq healthy CD8+ T cellsGroups 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.
Summary (written by the submitters)
Gain-of-function (GOF) variants in STAT3 cause a complex disorder characterized by early-onset autoimmunity, lymphoproliferation, recurrent infections, and immune dysregulation. In both primary human and mouse models of STAT3 GOF, CD8+ T cells have been implicated as pathogenic drivers of autoimmunity, though the exact mechanisms remain poorly understood.
Read the full summary ↓
Here, we found that in patients with STAT3 GOF, CD8+ T cells exist in a phenotypically activated state. Functional assessment revealed that naïve CD8+ T cells have an increased capacity for IFN-g and TNF-a production, with evidence of a Type I/II IFN transcriptional signature. Changes in immunoregulatory pathways revealed dysregulation of the purinergic signaling axis on CD8+ T cells: while CD39 was increased, downstream purinergic family members, CD73 and the adenosine receptor, A2AR, were downregulated, impairing the potential to produce or sense immunosuppressive adenosine. Evaluation of the impact of precision therapy in the form of JAK inhibitors at a cellular and functional level revealed partial normalization of naïve CD8+ T cell dysregulation, including aberrant cytokine production in patients. Our study suggests that a dysregulated purinergic signaling axis plays a key role in CD8+ T cell dysregulation in STAT3 GOF and may have implications for other rare monogenic immune disorders and common inflammatory disorders.
This dataset
Open GSE311536 in finder → Find more human 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 GSE311536_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 PRJNA1369624 and SRA study SRP649013. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
7 × scRNAseq STAT3GOF CD8+ T cells vs 7 × scTCRseq STAT3GOF CD8+ T cells vs 5 × scRNAseq healthy CD8+ T cells vs 5 × scTCRseq healthy CD8+ T cells

Supports a between-group comparison across 24 samples.

How we read this: 4 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
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