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

被引：6

作者：

Delacher, Michael ^{[1
,2
,3
]}

Barra, Melanie M. ^{[3
]}

Herzig, Yonatan ^{[4
]}

Eichelbaum, Katrin ^{[5
]}

Rafiee, Mahmoud-Reza ^{[5
]}

Richards, David M. ^{[3
]}

Traeger, Ulrike ^{[3
]}

Hofer, Ann-Cathrin ^{[3
]}

Kazakov, Alexander ^{[3
]}

Braband, Kathrin L. ^{[3
]}

Gonzalez, Marina ^{[3
]}

Woehrl, Lukas ^{[2
]}

Schambeck, Kathrin ^{[2
]}

Imbusch, Charles D. ^{[6
,7
]}

Abramson, Jakub ^{[4
]}

Krijgsveld, Jeroen ^{[5
,8
,9
]}

Feuerer, Markus ^{[1
,2
,3
]}

机构：

[1] Regensburg Univ, Chair Immunol, Franz Josef Strauss Allee 11, D-93053 Regensburg, Germany

[2] Regensburg Ctr Intervent Immunol RCI, Franz Josef Strauss Allee 11, D-93053 Regensburg, Germany

[3] German Canc Res Ctr, Tumor Immunol Program, Immune Tolerance Grp, Neuenheimer Feld 280, D-69120 Heidelberg, Germany

[4] Weizmann Inst Sci, Dept Immunol, 234 Herzl St, IL-76100 Rehovot, Israel

[5] European Mol Biol Lab, Meyerhofstr 1, D-69117 Heidelberg, Germany

[6] Heidelberg Univ, Fac Biosci, Neuenheimer Feld 234, D-69120 Heidelberg, Germany

[7] German Canc Res Ctr, Div Appl Bioinformat, Neuenheimer Feld 581, D-69120 Heidelberg, Germany

[8] German Canc Res Ctr, Prote Stem Cells & Canc, Neuenheimer Feld 581, D-69120 Heidelberg, Germany

[9] Heidelberg Univ, Med Fac, Neuenheimer Feld 672, D-69120 Heidelberg, Germany

来源：

ISCIENCE | 2020年 / 23卷 / 05期

基金：

欧洲研究理事会;

关键词：

INDUCTION; PROTEIN; ENTEROPATHY; ENHANCER; SMAD3; GENE;

D O I：

10.1016/j.isci.2020.101127

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：41

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