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Quantitative proteomics identifies TCF1 as a negative regulator of Foxp3 expression in conventional T cells

Regulatory T cells are important regulators of the immune system and have versatile functions for the homeostasis and repair of tissues. They express the forkhead box transcription factor Foxp3 as a lineage-defining protein. Negative regulators of Foxp3 expression are not well understood. Here, we g...

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Main Authors: Delacher, Michael (Author) , Barra, Melanie M. (Author) , Herzig, Yonatan (Author) , Eichelbaum, Katrin (Author) , Rafiee, Mahmoud-Reza (Author) , Richards, David (Author) , Träger, Ulrike (Author) , Hofer, Ann-Cathrin (Author) , Kazakov, Alexander (Author) , Braband, Kathrin L. (Author) , Gonzalez, Marina (Author) , Wöhrl, Lukas (Author) , Schambeck, Kathrin (Author) , Imbusch, Charles (Author) , Abramson, Jakub (Author) , Krijgsveld, Jeroen (Author) , Feuerer, Markus (Author)
Format: Article (Journal)
Language:English
Published: May 22, 2020
In: iScience
Year: 2020, Volume: 23, Issue: 5, Pages: 1-15
ISSN:2589-0042
DOI:10.1016/j.isci.2020.101127
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.isci.2020.101127
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S2589004220303126
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Author Notes:Michael Delacher, Melanie M. Barra, Yonatan Herzig, Katrin Eichelbaum, Mahmoud-Reza Rafiee, David M. Richards, Ulrike Träger, Ann-Cathrin Hofer, Alexander Kazakov, Kathrin L. Braband, Marina Gonzalez, Lukas Wöhrl, Kathrin Schambeck, Charles D. Imbusch, Jakub Abramson, Jeroen Krijgsveld, and Markus Feuerer
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Summary:Regulatory T cells are important regulators of the immune system and have versatile functions for the homeostasis and repair of tissues. They express the forkhead box transcription factor Foxp3 as a lineage-defining protein. Negative regulators of Foxp3 expression are not well understood. Here, we generated double-stranded DNA probes complementary to the Foxp3 promoter sequence and performed a pull-down with nuclear protein in vitro, followed by elution of bound proteins and quantitative mass spectrometry. Of the Foxp3-promoter-binding transcription factors identified with this approach, one was T cell factor 1 (TCF1). Using viral over-expression, we identified TCF1 as a repressor of Foxp3 expression. In TCF1-deficient animals, increased levels of Foxp3intermediateCD25negative T cells were identified. CRISPR-Cas9 knockout studies in primary human and mouse conventional CD4 T (Tconv) cells revealed that TCF1 protects Tconv cells from inadvertent Foxp3 expression. Our data implicate a role of TCF1 in suppressing Foxp3 expression in activated T cells.
Item Description:Gesehen am 29.03.2021
Physical Description:Online Resource
ISSN:2589-0042
DOI:10.1016/j.isci.2020.101127

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