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Transcription Factor 7 Limits Regulatory T Cell Generation in the Thymus

Barra, Melanie M; Richards, David M; Hansson, Jenny LU ; Hofer, Ann-Cathrin; Delacher, Michael; Hettinger, Jan; Krijgsveld, Jeroen and Feuerer, Markus (2015) In Journal of Immunology 195(7). p.70-3058
Abstract

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... (More)

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.

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published
subject
keywords
Animals, Cell Lineage, Cell Proliferation, Forkhead Transcription Factors, Gene Expression Profiling, Hematopoiesis, Hepatocyte Nuclear Factor 1-alpha, Mice, Mice, Inbred C57BL, Mice, Knockout, Proteome, Signal Transduction, T-Lymphocytes, Regulatory, Thymus Gland, beta Catenin
in
Journal of Immunology
volume
195
issue
7
pages
13 pages
publisher
American Association of Immunologists
external identifiers
  • Scopus:84942428185
ISSN
1550-6606
DOI
10.4049/jimmunol.1500821
language
English
LU publication?
no
id
87f91d95-404c-4efe-8542-11b16ed77ff2
date added to LUP
2016-04-19 10:17:19
date last changed
2016-10-13 05:06:37
@misc{87f91d95-404c-4efe-8542-11b16ed77ff2,
  abstract     = {<p>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.</p>},
  author       = {Barra, Melanie M and Richards, David M and Hansson, Jenny and Hofer, Ann-Cathrin and Delacher, Michael and Hettinger, Jan and Krijgsveld, Jeroen and Feuerer, Markus},
  issn         = {1550-6606},
  keyword      = {Animals,Cell Lineage,Cell Proliferation,Forkhead Transcription Factors,Gene Expression Profiling,Hematopoiesis,Hepatocyte Nuclear Factor 1-alpha,Mice,Mice, Inbred C57BL,Mice, Knockout,Proteome,Signal Transduction,T-Lymphocytes, Regulatory,Thymus Gland,beta Catenin},
  language     = {eng},
  month        = {10},
  number       = {7},
  pages        = {70--3058},
  publisher    = {ARRAY(0xa66fd28)},
  series       = {Journal of Immunology},
  title        = {Transcription Factor 7 Limits Regulatory T Cell Generation in the Thymus},
  url          = {http://dx.doi.org/10.4049/jimmunol.1500821},
  volume       = {195},
  year         = {2015},
}