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

iScience

卷:23

Markus Feuerer¹  Yonatan Herzig²  Melanie M. Barra³  Michael Delacher⁴  Mahmoud-Reza Rafiee⁵  Ulrike Träger⁶  David M. Richards⁶  Jeroen Krijgsveld⁷  Alexander Kazakov⁸  Kathrin Schambeck⁸  Ann-Cathrin Hofer⁸  Kathrin L. Braband⁸  Marina Gonzalez⁸  Lukas Wöhrl⁸  Katrin Eichelbaum⁸  Charles D. Imbusch⁹  Jakub Abramson⁹ 

[1] Division of Applied Bioinformatics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120 Heidelberg, Germany;

[2] Immune Tolerance Group, Tumor Immunology Program, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany;

[3] Regensburg Center for Interventional Immunology (RCI), Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany;

[4] Chair for Immunology, Regensburg University, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany;

[5] Department of Immunology, Weizmann Institute of Science, 234 Herzl Street, 76100 Rehovot, Israel;

[6] European Molecular Biology Laboratory, Meyerhofstraße 1, 69117 Heidelberg, Germany;

[7] Faculty of Biosciences, Heidelberg University, Im Neuenheimer Feld 234, 69120 Heidelberg, Germany;

关键词: Molecular Biology;    Molecular Mechanism of Gene Regulation;    Immunology;    Proteomics;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: 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.

【 授权许可】

Unknown