The Transcription Factor Tcf1 Contributes to Normal NK Cell Development and Function by Limiting the Expression of Granzymes.

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Serval ID
serval:BIB_87F6877665CF
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The Transcription Factor Tcf1 Contributes to Normal NK Cell Development and Function by Limiting the Expression of Granzymes.
Journal
Cell reports
Author(s)
Jeevan-Raj B., Gehrig J., Charmoy M., Chennupati V., Grandclément C., Angelino P., Delorenzi M., Held W.
ISSN
2211-1247 (Electronic)
Publication state
Published
Issued date
18/07/2017
Peer-reviewed
Oui
Volume
20
Number
3
Pages
613-626
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
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.
Keywords
Animals, Gene Expression Regulation, Enzymologic/immunology, Granzymes/genetics, Granzymes/immunology, Hepatocyte Nuclear Factor 1-alpha/genetics, Hepatocyte Nuclear Factor 1-alpha/immunology, Killer Cells, Natural/immunology, Mice, Mice, Knockout, NK cells, T cell factor 1, Tcf1, granzyme B, self-destruction
Pubmed
Web of science
Open Access
Yes
Create date
04/09/2017 10:20
Last modification date
04/05/2021 5:36
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