Omics · study · 2026
Mitochondrial Calcium Uniporter modulates CD8+ T cell stemness programs and regulates alloimmunity [RNAseq 1]
Listed in NCBI GEO
Stemness programs sustain the alloreactive CD8+ T cells pool in epithelial tissues to mediate graft-versus-host disease (GVHD).
Description
Despite suppressing T cell activation, pan Ca2+ signaling inhibition treatment retains stemness programs, and cannot prevent GVHD development in the chronic stage while enhances risks for tumor relapse and infection. Whether specific Ca2+ channels dictate T cell alloreactivity remains to be uncovered.
Here we show the mitochondrial calcium uniporter (MCU) regulates stemness programs in alloreactive CD8+ T cells. Genetic ablation of Mcu impaired the transcription of stemness genes and promoted alloreactive CD8+ T cell exhaustion development. Mechanistically, Mcu deficiency increased NF-κB activity during TCR stimulation, enhanced CD25 level hence the sensitivity to IL2.
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After activation, Mcu expression was intrinsically tuned back to baseline level. Ectopic expression of Mcu decreased the expression of pro-survival stemness genes and enhanced restimulation-induced cell death (RICD), abrogating alloreactive CD8+ T cell GVHD-inducing capacity. Pharmacological enhancement of MCU function with the FDA approved anti-malaria drug artesunate reduced GVHD but spared anti-leukemia potency.
These findings unravel MCU controls stemness programs in alloreactive CD8+ T cells, highlighting the translational potential of MCU-targeting genetic or pharmacological approaches in the modulation of T cell alloimmunity.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE306nnn/GSE306362 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE306362 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1310521 ncbi.nlm.nih.gov/bioproject/PRJNA1310521 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- Cancer 65% · Disease 75% · RNA sequencing 65%
Provenance · 1 source records, 10 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE306362 | 15 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:cancer | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[disease].local:disease:disease | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| 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[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| 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 |