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RIPK3 promotes neuronal survival by suppressing excitatory neurotransmission during CNS viral infection

GSE264436 Mus musculus (mouse) RNA-seq (gene expression) 18 samples Submitted 2025/02/03 Platform GPL21103
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 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
The kinase RIPK3 promotes neuronal survival by suppressing excitatory neurotransmission during central nervous system viral infectionImmunity · 2025
Summary (written by the submitters)
While recent work has identified roles for cytokines and inflammation in the regulation of neural activity, the capacity for cell intrinsic innate immune signaling within neurons to influence neurotransmission remains poorly understood. However, the existing evidence linking immune signaling with neuronal activity suggests that modulation of neurotransmission may serve previously undefined roles in host protection and pathogen control within the central nervous system.
Read the full summary ↓
Here, we identify a specialized function for RIPK3, a kinase traditionally associated with necroptotic cell death, in preserving neuronal survival during neurotropic flavivirus infection through the suppression of excitatory neurotransmission. We show that RIPK3 coordinates transcriptomic changes in neurons that suppress neuronal glutamate signaling, thereby desensitizing neurons to excitotoxic cell death. These effects occur independently of the traditional functions of RIPK3 in promoting MLKL-dependent necroptosis and NFκB-mediated inflammatory transcription. Instead, RIPK3 promotes phosphorylation of the key neural regulatory kinase CAMKII, which in turn activates the transcription factor CREB to drive a neuroprotective transcriptional program and suppress deleterious glutamatergic signaling. These findings identify an unexpected function for a canonical cell death protein in promoting neuronal survival during viral infection through the modulation of neuronal activity, highlighting new mechanisms of neuroimmune crosstalk.
Published in
The kinase RIPK3 promotes neuronal survival by suppressing excitatory neurotransmission during central nervous system viral infection
Estevez I, Buckley BD, Lindman M et al. · Immunity 2025 · PMID 39999836 · doi:10.1016/j.immuni.2025.01.017
This dataset
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.

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 GSE264436_RAW.tar (it can run to tens of gigabytes).

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.

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 PRJNA1102407 and SRA study SRP502921. Searching any of these in the dataset finder brings you back here.

Study design
6 conditions, mostly in triplicate
Neuron, control, ×3 Neuron, BB, ×3 Neuron, CREB inh, ×3 Neuron, CaMKII inh, ×3 Neuron, BB, CREB inh, ×3 Neuron, BB, CaMKII inh, ×3

Supports a between-group comparison across 18 samples.

How we read this: 6 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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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.