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Loss of Sphingosine-1-Phosphate Receptor 4 weakens innate mechanisms leading to defective lymph node hypertrophy and germinal center formation

GSE266438 Mus musculus (mouse) RNA-seq (gene expression) 45 samples Submitted 2024/08/02 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 45 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
45 samples: 8 conditions, mostly with about 6 replicates eachGroups 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
Sphingosine-1-Phosphate Receptor 4 links neutrophils and early local inflammation to lymphocyte recruitment into the draining lymph node to facilitate robust germinal center formationFrontiers in immunology · 2024
Summary (written by the submitters)
The successful development of germinal centers (GC) relies heavily on innate mechanisms to amplify the initial inflammatory cascade. In addition to their role in antigen presentation, innate cells are essential for redirection of circulating lymphocytes toward the draining lymph node (dLN) to maximize antigen-surveillance and identification of cognate lymphocytes.
Read the full summary ↓
Sphingosine-1-phosphate (S1P) and its receptors (S1PR1-5) regulate various aspects of immunity, however, the role of S1PR4 in adaptive responses is not well understood. Here we use a localized TH1 footpad immunization model to carefully monitor changes in immune populations within circulation, the immunization site, and the dLN. We found that mice lacking S1PR4 ultimately developed attenuated GC and activation pathways due in part to upstream defects in neutrophil activity. Within hours of immunization, failed neutrophil mobilization and infiltration into the tissue of S1PR4-/- mice resulted in reduced local inflammation and vascular changes. Using depletion antibodies, we show that neutrophils were necessary to facilitate the early edema as well as the redirection of circulating lymphocytes into the dLN, thereby contributing to reduced dLN hypertrophy in S1PR4-/-. Using in vivo adoptive transfer, we demonstrated that these homing deficiencies were not lymphocyte-intrinsic but instead due to microenvironment failures within the S1PR4-/- host. Consistent with the known role of lymphocyte entry promoting DC emigration, the dLN of these mice exhibited defects in the prolonged but not early accumulation of DC. This was accompanied by inadequate growth of the vascular network, and reduced expression of the leukocyte tethering ligand, PNAd, within high endothelial venule (HEV) regions, all of which can contribute to LN expansion. Overall, our study reveals that S1PR4 plays an important amplifying role during the early innate response that affects the magnitude of a downstream GC reaction.
Published in
Sphingosine-1-Phosphate Receptor 4 links neutrophils and early local inflammation to lymphocyte recruitment into the draining lymph node to facilitate robust germinal center formation
Luker AJ, Wukitch A, Kulinski JM et al. · Frontiers in immunology 2024 · PMID 39188715 · doi:10.3389/fimmu.2024.1427509
This dataset
Open GSE266438 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 GSE266438_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 PRJNA1107179 and SRA study SRP505424. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39188715) ↗
Study design
8 conditions, mostly with about 6 replicates each
Tfh CD4 T-cells, ×6 Tfh CD4 T-cells, S1PR4 KO, ×6 non-Tfh CD4 T-cells, ×6 non-Tfh CD4 T-cells, S1PR4 KO, ×6 Germinal center B-cells, ×6 Germinal center B-cells, S1PR4 KO, ×6 non-Germinal center B-cells, ×5 non-Germinal center B-cells, S1PR4 KO, ×4

Supports a between-group comparison across 45 samples.

How we read this: 8 replicated groups read from 45 sample titles; they account for 45 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

+ 5 more — browse all 45 samples with per-sample file links →

Datasets on a similar topic

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