GEO series

The C3-C3aR axis modulates trained immunity in alveolar macrophages

GSE281001 Mus musculus (mouse) RNA-seq (gene expression) 8 samples Submitted 2026/08/07 Platform GPL24247

At a glance

RNA-seq (gene expression) · mouse · 8 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: 8 samples: 4 × WT_trained vs 4 × C3KO_trainedGroups 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)

Complement protein C3 is crucial for immune responses in mucosal sites like the respiratory system, where it aids in microbe elimination and enhances inflammation. While trained immunity – enhanced secondary responses of innate immune cells after prior exposure – is well-studied, the role of the complement system in trained immune responses remains unclear.

Read the full summary ↓

We investigated the role of C3 in trained immunity and found that in vivo, trained wild-type mice showed significantly elevated pro-inflammatory cytokines and increased C3a levels upon a second stimulus, whereas C3-deficient mice exhibited a blunted cytokine response and heightened evidence of lung injury. Ex vivo, C3-deficient alveolar macrophages (AMs) displayed reduced chemokine and cytokine output after training, which was restored by exogenous C3 but not by C3a. Inhibiting C3aR, both pharmacologically and with a genetic C3aR knockout, prevented this restoration, indicating the necessity of C3aR engagement. Mechanistically, trained WT AMs demonstrated enhanced glycolytic activity compared to C3-deficient AMs – a defect corrected by exogenous C3 in a C3aR-dependent manner. These findings reveal that C3 modulates trained immunity in AMs through C3aR signaling, affecting cytokine production and metabolic reprogramming, and highlight a novel role for C3 in trained immunity.

This dataset

Open GSE281001 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 GSE281001_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 PRJNA1181815 and SRA study SRP543091. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

4 × WT_trained vs 4 × C3KO_trained

Supports a between-group comparison across 8 samples.

How we read this: 2 replicated groups read from 8 sample titles; they account for 8 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

GSM8608639 WT_trained_1 WT_trained
GSM8608640 WT_trained_2 WT_trained
GSM8608641 WT_trained_3 WT_trained
GSM8608642 WT_trained_4 WT_trained
GSM8608643 C3KO_trained_1 C3KO_trained
GSM8608644 C3KO_trained_2 C3KO_trained
GSM8608645 C3KO_trained_3 C3KO_trained
GSM8608646 C3KO_trained_4 C3KO_trained

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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.