@article{d55bec5853034b8d8af0355fba5eeeed,
title = "Quantitative Proteomics Identifies TCF1 as a Negative Regulator of Foxp3 Expression in Conventional T Cells",
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.",
author = "Michael Delacher and Barra, {Melanie M.} and Yonatan Herzig and Katrin Eichelbaum and Mahmoud-Reza Rafiee and Richards, {David M.} and Ulrike Traeger and Ann-Cathrin Hofer and Alexander Kazakov and Braband, {Kathrin L.} and Marina Gonzalez and Lukas Woehrl and Kathrin Schambeck and Imbusch, {Charles D.} and Jakub Abramson and Jeroen Krijgsveld and Markus Feuerer",
note = "The Foxp3 promoter Luciferase vector was a kind gift of Prof. Dr. Akihiko Yoshimura (Keio University, Japan). TCF1-deficient animals were a gift from Prof. Dr. Hans Clevers (Hubrecht Institute, Utrecht, The Netherlands). We thank the DKFZ core facilities Preclinical Research, Flow Cytometry, and Genomics & Proteomics, and the RCI flow cytometry core facility for technical support. We thank Sabine Schmitt (DKFZ), Marina Wuttke, Brigitte Ruhland, K.S., and Veronika Hofmann (all RCI) for technical support. We thank Dr. Simone Thomas for help with human samples. This work was supported by grants from the European Research Council (ERC-CoG, #648145 REGiREG) to M.F., and by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)—Projektnummer 324392634—TRR 221 to M.F., M.D. was supported by the German-Israeli Helmholtz Research School in Cancer Biology. Author contributions - M.D., M.M.B., J.K., J.A., and M.F. designed experiments; M.D., M.M.B., Y.H., K.E., M.-R.R., D.M.R., U.T., A.-C.H., A.K., K.L.B., M.G.., L.W., and K.S. performed the experiments; M.D., K.E., C.D.I., J.A., J.K., and M.F. analyzed data; M.D. and M.F. wrote the manuscript.",
year = "2020",
month = may,
day = "22",
doi = "10.1016/j.isci.2020.101127",
language = "الإنجليزيّة",
volume = "23",
journal = "iScience",
issn = "2589-0042",
publisher = "Elsevier",
number = "5",
}