Pyrimidine de novo synthesis inhibition selectively blocks effector but not memory T cell development.
Détails
ID Serval
serval:BIB_37BBC13C5B60
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Pyrimidine de novo synthesis inhibition selectively blocks effector but not memory T cell development.
Périodique
Nature immunology
ISSN
1529-2916 (Electronic)
ISSN-L
1529-2908
Statut éditorial
Publié
Date de publication
03/2023
Peer-reviewed
Oui
Volume
24
Numéro
3
Pages
501-515
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
Blocking pyrimidine de novo synthesis by inhibiting dihydroorotate dehydrogenase is used to treat autoimmunity and prevent expansion of rapidly dividing cell populations including activated T cells. Here we show memory T cell precursors are resistant to pyrimidine starvation. Although the treatment effectively blocked effector T cells, the number, function and transcriptional profile of memory T cells and their precursors were unaffected. This effect occurred in a narrow time window in the early T cell expansion phase when developing effector, but not memory precursor, T cells are vulnerable to pyrimidine starvation. This vulnerability stems from a higher proliferative rate of early effector T cells as well as lower pyrimidine synthesis capacity when compared with memory precursors. This differential sensitivity is a drug-targetable checkpoint that efficiently diminishes effector T cells without affecting the memory compartment. This cell fate checkpoint might therefore lead to new methods to safely manipulate effector T cell responses.
Mots-clé
Pyrimidines, Cell Cycle, Cell Differentiation
Pubmed
Web of science
Open Access
Oui
Création de la notice
28/02/2023 14:53
Dernière modification de la notice
16/11/2023 7:10