Omics · study · 2026
Control of naive T cell reactivity and peripheral tolerance by ascorbate and TET activity [RNA Slc23a2KO]
Listed in NCBI GEO
Maintenance of T cell naïve (Tn) state and restricting effector T cell differentiation upon basal level stimulations would be critical for immune homeostasis and prevention of autoimmunity.
Description
To understand how Tn state is regulated by nutrient cues in a cell-intrinsic manner, here we perform an in vivo CRISPR screening to identify required solute carrier (SLC) proteins that transport metabolites and ions into T cells. Among SLC proteins revealed by this experiment, vitamin C transporter Slc23a2 appears to play a role.
Conditional ablation of Slc23a2 in T cells by genetic approaches reduces intracellular vitamin C levels by approximately 80%, accompanied by spontaneous activation and differentiation of Tn cells, autoantibody production, and autoimmune pathology in select organs. Slc23a2-deficient Tn cells exhibit profound DNA hypermethylation, dysregulation of genes controlling signaling transduction and transcription, and enhanced differentiation of helper T cells upon stimulation.
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These results define a broad regulatory space of vitamin C as a cofactor of Tet enzymes in controlling active DNA demethylation. In agreement, conditional deletion of Tet genes impairs Tn state and increases helper T cell differentiation. Thus, our study reveals a cell-intrinsic mechanism by which micronutrient vitamin C via Slc23a2 maintains Tn state and self-tolerance by promoting Tet-mediated DNA demethylation.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE225nnn/GSE225325 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE225325 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA935261 ncbi.nlm.nih.gov/bioproject/PRJNA935261 ↗
project · from NCBI GEO
- PubMed 42308298 pubmed.ncbi.nlm.nih.gov/42308298 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
Provenance · 1 source records, 7 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE225325 | 12 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:10090 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |