Delacher, Michael and Barra, Melanie M. and Herzig, Yonatan and Eichelbaum, Katrin and Rafiee, Mahmoud-Reza and Richards, David M. and Traeger, Ulrike and Hofer, Ann-Cathrin and Kazakov, Alexander and Braband, Kathrin L. and Gonzalez, Marina and Woehrl, Lukas and Schambeck, Kathrin and Imbusch, Charles D. and Abramson, Jakub and Krijgsveld, Jeroen and Feuerer, Markus (2020) Quantitative Proteomics Identifies TCF1 as a Negative Regulator of Foxp3 Expression in Conventional T Cells. ISCIENCE, 23 (5): 101127. ISSN , 2589-0042
Full text not available from this repository. (Request a copy)Abstract
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 Foxp3(intermediate)CD25(negative) T cells were identified. CRISPR-Cas9 knockout studies in primary human and mouse conventional CD4 T (T-conv) cells revealed that TCF1 protects T-conv cells from inadvertent Foxp3 expression. Our data implicate a role of TCF1 in suppressing Foxp3 expression in activated T cells.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INDUCTION; PROTEIN; ENTEROPATHY; ENHANCER; SMAD3; GENE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Immunologie Medicine > Zentren des Universitätsklinikums Regensburg > Regensburger Centrum für Interventionelle Immunologie (RCI) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 23 Mar 2021 11:31 |
| Last Modified: | 23 Mar 2021 11:31 |
| URI: | https://pred.uni-regensburg.de/id/eprint/44535 |
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