TY  - JOUR
AU  - Delacher, Michael
AU  - Barra, Melanie M
AU  - Herzig, Yonatan
AU  - Eichelbaum, Katrin
AU  - Rafiee, Mahmoud-Reza
AU  - Richards, David M
AU  - Träger, Ulrike
AU  - Hofer, Ann-Cathrin
AU  - Kazakov, Alexander
AU  - Braband, Kathrin
AU  - Gonzalez, Marina
AU  - Wöhrl, Lukas
AU  - Schambeck, Kathrin
AU  - Imbusch, Charles D
AU  - Abramson, Jakub
AU  - Krijgsveld, Jeroen
AU  - Feuerer, Markus
TI  - Quantitative Proteomics Identifies TCF1 as a Negative Regulator of Foxp3 Expression in Conventional T Cells.
JO  - iScience
VL  - 23
IS  - 5
SN  - 2589-0042
CY  - St. Louis
PB  - Elsevier
M1  - DKFZ-2020-01311
SP  - 101127
PY  - 2020
N1  - #EA:D100#LA:D100#
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:32422593
C2  - pmc:PMC7229326
DO  - DOI:10.1016/j.isci.2020.101127
UR  - https://inrepo02.dkfz.de/record/157014
ER  -