Quantitative Proteomics Identifies TCF1 as a Negative Regulator of Foxp3 Expression in Conventional T Cells.

Autor: Delacher M; Chair for Immunology, Regensburg University, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany; Regensburg Center for Interventional Immunology (RCI), Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany; Immune Tolerance Group, Tumor Immunology Program, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany., Barra MM; Immune Tolerance Group, Tumor Immunology Program, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany., Herzig Y; Department of Immunology, Weizmann Institute of Science, 234 Herzl Street, 76100 Rehovot, Israel., Eichelbaum K; European Molecular Biology Laboratory, Meyerhofstraße 1, 69117 Heidelberg, Germany., Rafiee MR; European Molecular Biology Laboratory, Meyerhofstraße 1, 69117 Heidelberg, Germany., Richards DM; Immune Tolerance Group, Tumor Immunology Program, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany., Träger U; Immune Tolerance Group, Tumor Immunology Program, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany., Hofer AC; Immune Tolerance Group, Tumor Immunology Program, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany., Kazakov A; Immune Tolerance Group, Tumor Immunology Program, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany., Braband KL; Immune Tolerance Group, Tumor Immunology Program, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany., Gonzalez M; Immune Tolerance Group, Tumor Immunology Program, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany., Wöhrl L; Regensburg Center for Interventional Immunology (RCI), Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany., Schambeck K; Regensburg Center for Interventional Immunology (RCI), Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany., Imbusch CD; Faculty of Biosciences, Heidelberg University, Im Neuenheimer Feld 234, 69120 Heidelberg, Germany; Division of Applied Bioinformatics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120 Heidelberg, Germany., Abramson J; Department of Immunology, Weizmann Institute of Science, 234 Herzl Street, 76100 Rehovot, Israel., Krijgsveld J; European Molecular Biology Laboratory, Meyerhofstraße 1, 69117 Heidelberg, Germany; Proteomics of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120 Heidelberg, Germany; Medical Faculty, Heidelberg University, Im Neuenheimer Feld 672, 69120 Heidelberg, Germany., Feuerer M; Chair for Immunology, Regensburg University, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany; Regensburg Center for Interventional Immunology (RCI), Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany; Immune Tolerance Group, Tumor Immunology Program, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. Electronic address: markus.feuerer@ukr.de.
Jazyk: angličtina
Zdroj: IScience [iScience] 2020 May 22; Vol. 23 (5), pp. 101127. Date of Electronic Publication: 2020 May 04.
DOI: 10.1016/j.isci.2020.101127
Abstrakt: 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.
Competing Interests: Declaration of Interests The authors declare no competing financial interests.
(Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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