Titre
The Transcription Factor Tcf1 Contributes to Normal NK Cell Development and Function by Limiting the Expression of Granzymes.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Jeevan-Raj, B.
Auteure/Auteur
Gehrig, J.
Auteure/Auteur
Charmoy, M.
Auteure/Auteur
Chennupati, V.
Auteure/Auteur
Grandclément, C.
Auteure/Auteur
Angelino, P.
Auteure/Auteur
Delorenzi, M.
Auteure/Auteur
Held, W.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
2211-1247
Statut éditorial
Publié
Date de publication
2017-07-18
Volume
20
Numéro
3
Première page
613
Dernière page/numéro d’article
626
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Résumé
The transcription factor Tcf1 is essential for the development of natural killer (NK) cells. However, its precise role has not been clarified. Our combined analysis of Tcf1-deficient and transgenic mice indicated that Tcf1 guides NK cells through three stages of development. Tcf1 expression directed bone marrow progenitors toward the NK cell lineage and ensured the survival of NK-committed cells, and its downregulation was needed for terminal maturation. Impaired survival of NK-committed cells was due to excessive expression of granzyme B (GzmB) and other granzyme family members, which induced NK cell self-destruction during maturation and following activation with cytokines or target cells. Mechanistically, Tcf1 binding reduced the activity of a Gzmb-associated regulatory element, and this accounted for the reduced Gzmb expression in Tcf1-expressing NK cells. These data identify an unexpected requirement to limit the expression of cytotoxic effector molecules for the normal expansion and function of NK cells.
PID Serval
serval:BIB_87F6877665CF
PMID
Open Access
Oui
Date de création
2017-09-04T09:20:33.154Z
Date de création dans IRIS
2025-05-21T01:35:07Z
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Nom
1-s2.0-S2211124717309026-main.pdf
Version du manuscrit
published
Taille
5.02 MB
Format
Adobe PDF
PID Serval
serval:BIB_87F6877665CF.P001
URN
urn:nbn:ch:serval-BIB_87F6877665CF1
Somme de contrôle
(MD5):8ba6c2bde26d2185279514768e708f9f