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

Michael Delacher1, Melanie M Barra2, Yonatan Herzig3

  • 1Chair 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.

Iscience
|May 19, 2020
PubMed

Insights

T-cell factor 1 (TCF1) suppresses the expression of Foxp3 in T cells. This finding reveals TCF1

Area of Science:

  • Immunology
  • Molecular Biology
  • Cellular Biology

Background:

  • Regulatory T cells (Tregs) are crucial for immune homeostasis and tissue repair.
  • The transcription factor Foxp3 defines the Treg lineage.
  • Mechanisms negatively regulating Foxp3 expression remain largely unknown.

Purpose of the Study:

  • To identify novel negative regulators of Foxp3 expression.
  • To elucidate the role of T-cell factor 1 (TCF1) in Foxp3 regulation.

Main Methods:

  • In vitro pull-down assays using Foxp3 promoter DNA probes and nuclear proteins.
  • Quantitative mass spectrometry to identify binding proteins.
  • Viral overexpression and CRISPR-Cas9 gene editing in human and mouse T cells.

Main Results:

  • T-cell factor 1 (TCF1) was identified as a Foxp3 promoter-binding transcription factor.
  • TCF1 acts as a repressor of Foxp3 expression.
  • TCF1 deficiency leads to increased Foxp3 expression in specific T cell subsets.
  • TCF1 protects conventional CD4 T cells from unintended Foxp3 induction.

Conclusions:

  • T-cell factor 1 (TCF1) plays a significant role in suppressing Foxp3 expression.
  • TCF1 prevents inappropriate Foxp3 activation in conventional T cells.
  • TCF1 is implicated in maintaining T cell homeostasis by limiting Foxp3 induction.
Keywords:
ImmunologyMolecular BiologyMolecular Mechanism of Gene RegulationProteomics

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