Type 1 interferons and Foxo1 down-regulation play a key role in age-related T-cell exhaustion in mice.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
26 Feb 2024
26 Feb 2024
Historique:
received:
19
12
2022
accepted:
05
02
2024
medline:
27
2
2024
pubmed:
27
2
2024
entrez:
26
2
2024
Statut:
epublish
Résumé
Foxo family transcription factors are critically involved in multiple processes, such as metabolism, quiescence, cell survival and cell differentiation. Although continuous, high activity of Foxo transcription factors extends the life span of some species, the involvement of Foxo proteins in mammalian aging remains to be determined. Here, we show that Foxo1 is down-regulated with age in mouse T cells. This down-regulation of Foxo1 in T cells may contribute to the disruption of naive T-cell homeostasis with age, leading to an increase in the number of memory T cells. Foxo1 down-regulation is also associated with the up-regulation of co-inhibitory receptors by memory T cells and exhaustion in aged mice. Using adoptive transfer experiments, we show that the age-dependent down-regulation of Foxo1 in T cells is mediated by T-cell-extrinsic cues, including type 1 interferons. Taken together, our data suggest that type 1 interferon-induced Foxo1 down-regulation is likely to contribute significantly to T-cell dysfunction in aged mice.
Identifiants
pubmed: 38409097
doi: 10.1038/s41467-024-45984-8
pii: 10.1038/s41467-024-45984-8
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1718Subventions
Organisme : Fondation pour la Recherche Médicale (Foundation for Medical Research in France)
ID : EQU202103012662
Informations de copyright
© 2024. The Author(s).
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