Suppression of Tcf1 by Inflammatory Cytokines Facilitates Effector CD8 T Cell Differentiation.

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Version: Final published version
Serval ID
serval:BIB_C287A133B463
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Suppression of Tcf1 by Inflammatory Cytokines Facilitates Effector CD8 T Cell Differentiation.
Journal
Cell reports
Author(s)
Danilo M., Chennupati V., Silva J.G., Siegert S., Held W.
ISSN
2211-1247 (Electronic)
Publication state
Published
Issued date
20/02/2018
Peer-reviewed
Oui
Volume
22
Number
8
Pages
2107-2117
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
The formation of central CD8 T cell memory in response to infection depends on the transcription factor Tcf1 (Tcf7). Tcf1 is expressed at high levels in naive CD8 T cells but downregulated in most CD8 T cells during effector differentiation. The relevance of Tcf1 downregulation for effector differentiation and the signals controlling Tcf1 expression have not been elucidated. Here, we show that systemic inflammatory signals downregulated Tcf1 in CD8 T cells during dendritic cell vaccination and bacterial infections. The suppressive effect was mediated by the inflammatory cytokine interleukin 12 (IL-12), which acted via STAT4 in CD8 T cells. IL-12-induced Tcf1 downregulation required cell cycling, occurred at the transcriptional level, and was prevented in part by inhibiting DNA methyltransferases. Absence of Tcf1 during T cell priming circumvented the need of systemic inflammation for effector differentiation. We conclude that silencing of Tcf1 by systemic inflammation facilitates effector CD8 T cell differentiation.
Keywords
Animals, CD8-Positive T-Lymphocytes/cytology, CD8-Positive T-Lymphocytes/metabolism, Cell Cycle, Cell Differentiation, Cell Division, Cross-Priming/immunology, Cytokines/metabolism, Down-Regulation/genetics, Gene Expression Regulation, Immunologic Memory, Inflammation/pathology, Inflammation Mediators/metabolism, Interleukin-12/metabolism, Interleukin-12 Receptor beta 2 Subunit/metabolism, Mice, Inbred C57BL, STAT4 Transcription Factor/metabolism, Signal Transduction, T Cell Transcription Factor 1/metabolism, Vaccination, CD8 T cells, DC vaccination, IL-12, STAT4, Tcf1, effector differentiation, inflammation, memory
Pubmed
Web of science
Open Access
Yes
Create date
01/03/2018 18:58
Last modification date
20/08/2019 16:37
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