Transcription Factor 7 Limits Regulatory T Cell Generation in the Thymus

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Transcription Factor 7 Limits Regulatory T Cell Generation in the Thymus. / Barra, Melanie M; Richards, David M; Hansson, Jenny; Hofer, Ann-Cathrin; Delacher, Michael; Hettinger, Jan; Krijgsveld, Jeroen; Feuerer, Markus.

In: Journal of Immunology, Vol. 195, No. 7, 01.10.2015, p. 3058-70.

Research output: Contribution to journalArticle

Harvard

Barra, MM, Richards, DM, Hansson, J, Hofer, A-C, Delacher, M, Hettinger, J, Krijgsveld, J & Feuerer, M 2015, 'Transcription Factor 7 Limits Regulatory T Cell Generation in the Thymus', Journal of Immunology, vol. 195, no. 7, pp. 3058-70. https://doi.org/10.4049/jimmunol.1500821

APA

Barra, M. M., Richards, D. M., Hansson, J., Hofer, A-C., Delacher, M., Hettinger, J., ... Feuerer, M. (2015). Transcription Factor 7 Limits Regulatory T Cell Generation in the Thymus. Journal of Immunology, 195(7), 3058-70. https://doi.org/10.4049/jimmunol.1500821

CBE

Barra MM, Richards DM, Hansson J, Hofer A-C, Delacher M, Hettinger J, Krijgsveld J, Feuerer M. 2015. Transcription Factor 7 Limits Regulatory T Cell Generation in the Thymus. Journal of Immunology. 195(7):3058-70. https://doi.org/10.4049/jimmunol.1500821

MLA

Vancouver

Barra MM, Richards DM, Hansson J, Hofer A-C, Delacher M, Hettinger J et al. Transcription Factor 7 Limits Regulatory T Cell Generation in the Thymus. Journal of Immunology. 2015 Oct 1;195(7):3058-70. https://doi.org/10.4049/jimmunol.1500821

Author

Barra, Melanie M ; Richards, David M ; Hansson, Jenny ; Hofer, Ann-Cathrin ; Delacher, Michael ; Hettinger, Jan ; Krijgsveld, Jeroen ; Feuerer, Markus. / Transcription Factor 7 Limits Regulatory T Cell Generation in the Thymus. In: Journal of Immunology. 2015 ; Vol. 195, No. 7. pp. 3058-70.

RIS

TY - JOUR

T1 - Transcription Factor 7 Limits Regulatory T Cell Generation in the Thymus

AU - Barra, Melanie M

AU - Richards, David M

AU - Hansson, Jenny

AU - Hofer, Ann-Cathrin

AU - Delacher, Michael

AU - Hettinger, Jan

AU - Krijgsveld, Jeroen

AU - Feuerer, Markus

N1 - Copyright © 2015 by The American Association of Immunologists, Inc.

PY - 2015/10/1

Y1 - 2015/10/1

N2 - Regulatory T cells (Tregs) differentiate in the thymus, but the mechanisms that control this process are not fully understood. We generated a comprehensive quantitative and differential proteome of murine Tregs and conventional T cells. We identified 5225 proteins, 164 of which were differentially expressed in Tregs. Together with the comparative analysis of proteome and gene expression data, we identified TCF7 as a promising candidate. Genetic elimination of transcription factor 7 (TCF7) led to increased fractions of Tregs in the thymus. Reduced levels of TCF7, found in the heterozygote, resulted in a greater potential for Treg precursors to differentiate into the Treg lineage. In contrast, activation of TCF7 through β-catenin had the opposite effect. TCF7 levels influenced the required TCR signaling strength of Treg precursors, and TCF7 deficiency broadened the repertoire and allowed lower TCR affinities to be recruited into the Treg lineage. FOXP3 was able to repress TCF7 protein expression. In summary, we propose a regulatory role for TCF7 in limiting access to the Treg lineage.

AB - Regulatory T cells (Tregs) differentiate in the thymus, but the mechanisms that control this process are not fully understood. We generated a comprehensive quantitative and differential proteome of murine Tregs and conventional T cells. We identified 5225 proteins, 164 of which were differentially expressed in Tregs. Together with the comparative analysis of proteome and gene expression data, we identified TCF7 as a promising candidate. Genetic elimination of transcription factor 7 (TCF7) led to increased fractions of Tregs in the thymus. Reduced levels of TCF7, found in the heterozygote, resulted in a greater potential for Treg precursors to differentiate into the Treg lineage. In contrast, activation of TCF7 through β-catenin had the opposite effect. TCF7 levels influenced the required TCR signaling strength of Treg precursors, and TCF7 deficiency broadened the repertoire and allowed lower TCR affinities to be recruited into the Treg lineage. FOXP3 was able to repress TCF7 protein expression. In summary, we propose a regulatory role for TCF7 in limiting access to the Treg lineage.

KW - Animals

KW - Cell Lineage

KW - Cell Proliferation

KW - Forkhead Transcription Factors

KW - Gene Expression Profiling

KW - Hematopoiesis

KW - Hepatocyte Nuclear Factor 1-alpha

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Proteome

KW - Signal Transduction

KW - T-Lymphocytes, Regulatory

KW - Thymus Gland

KW - beta Catenin

U2 - 10.4049/jimmunol.1500821

DO - 10.4049/jimmunol.1500821

M3 - Article

VL - 195

SP - 3058

EP - 3070

JO - Journal of immunology (Baltimore, Md. : 1950)

T2 - Journal of immunology (Baltimore, Md. : 1950)

JF - Journal of immunology (Baltimore, Md. : 1950)

SN - 1550-6606

IS - 7

ER -