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

Delacher M, Barra MM, Herzig Y, Eichelbaum K, Rafiee MR, Richards DM, Traeger U, Hofer AC, Kazakov A, Braband KL, Gonzalez M, Woehrl L, Schambeck K, Imbusch CD, Abramson J, Krijgsveld J, Feuerer M (2020)

Publication Type: Journal article

Publication year: 2020

Journal

iScience Elsevier

Book Volume: 23

Article Number: 101127

Journal Issue: 5

DOI: 10.1016/j.isci.2020.101127

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 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.

Involved external institutions

Universität Regensburg DE Germany (DE) Deutsches Krebsforschungszentrum (DKFZ) DE Germany (DE) Weizmann Institute of Science IL Israel (IL) European Molecular Biology Laboratory (EMBL) DE Germany (DE) Regensburg Center for Interventional Immunology DE Germany (DE) Ruprecht-Karls-Universität Heidelberg DE Germany (DE)

How to cite

APA:

Delacher, M., Barra, M.M., Herzig, Y., Eichelbaum, K., Rafiee, M.-R., Richards, D.M.,... Feuerer, M. (2020). Quantitative Proteomics Identifies TCF1 as a Negative Regulator of Foxp3 Expression in Conventional T Cells. iScience, 23(5). https://doi.org/10.1016/j.isci.2020.101127

MLA:

Delacher, Michael, et al. "Quantitative Proteomics Identifies TCF1 as a Negative Regulator of Foxp3 Expression in Conventional T Cells." iScience 23.5 (2020).

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