Glut3 promotes cellular O-GlcNAcylation as a distinctive tumor-supportive feature in Treg cells.
Glut3
O-GlcNAcylation
Regulatory T cells
Treg
Treg metabolism
Journal
Cellular & molecular immunology
ISSN: 2042-0226
Titre abrégé: Cell Mol Immunol
Pays: China
ID NLM: 101242872
Informations de publication
Date de publication:
28 Oct 2024
28 Oct 2024
Historique:
received:
26
04
2024
accepted:
10
10
2024
medline:
29
10
2024
pubmed:
29
10
2024
entrez:
29
10
2024
Statut:
aheadofprint
Résumé
Regulatory T cells (Tregs) establish dominant immune tolerance but obstruct tumor immune surveillance, warranting context-specific mechanistic insights into the functions of tumor-infiltrating Tregs (TIL-Tregs). We show that enhanced posttranslational O-linked N-acetylglucosamine modification (O-GlcNAcylation) of cellular factors is a molecular feature that promotes a tumor-specific gene expression signature and distinguishes TIL-Tregs from their systemic counterparts. We found that altered glucose utilization through the glucose transporter Glut3 is a major facilitator of this process. Treg-specific deletion of Glut3 abrogates tumor immune tolerance, while steady-state immune homeostasis remains largely unaffected in mice. Furthermore, by employing mouse tumor models and human clinical data, we identified the NF-κB subunit c-Rel as one such factor that, through Glut3-dependent O-GlcNAcylation, functionally orchestrates gene expression in Tregs at tumor sites. Together, these results not only identify immunometabolic alterations and molecular events contributing to fundamental aspects of Treg biology, specifically at tumor sites but also reveal tumor-specific cellular properties that can aid in the development of Treg-targeted cancer immunotherapies.
Identifiants
pubmed: 39468304
doi: 10.1038/s41423-024-01229-8
pii: 10.1038/s41423-024-01229-8
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : National Research Foundation of Korea (NRF)
ID : 4.24643.01
Informations de copyright
© 2024. The Author(s), under exclusive licence to CSI and USTC.
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