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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| Hauptverfasser: | , , , , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
May 22, 2020
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| In: |
iScience
Year: 2020, Jahrgang: 23, Heft: 5, Pages: 1-15 |
| ISSN: | 2589-0042 |
| DOI: | 10.1016/j.isci.2020.101127 |
| Online-Zugang: | 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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| Verfasserangaben: | 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 |
MARC
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| 245 | 1 | 0 | |a Quantitative proteomics identifies TCF1 as a negative regulator of Foxp3 expression in conventional T cells |c 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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| 520 | |a 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. | ||
| 650 | 4 | |a Immunology | |
| 650 | 4 | |a Molecular Biology | |
| 650 | 4 | |a Molecular Mechanism of Gene Regulation | |
| 650 | 4 | |a Proteomics | |
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