NDLI: Transcription Factor 7 Limits Regulatory T Cell Generation in the Thymus.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Barra, Melanie M. Feuerer, Markus Krijgsveld, Jeroen Hansson, Jenny Hofer, Ann-Cathrin Hettinger, Jan Richards, David M. Delacher, Michael
Description	Author Affiliation: Barra MM ( Immune Tolerance, Tumor Immunology Program, German Cancer Research Center, 69120 Heidelberg, Germany); Richards DM ( Immune Tolerance, Tumor Immunology Program, German Cancer Research Center, 69120 Heidelberg, Germany); Hansson J ( Genome Biology Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany.); Hofer AC ( Immune Tolerance, Tumor Immunology Program, German Cancer Research Center, 69120 Heidelberg, Germany); Delacher M ( Immune Tolerance, Tumor Immunology Program, German Cancer Research Center, 69120 Heidelberg, Germany); Hettinger J ( Immune Tolerance, Tumor Immunology Program, German Cancer Research Center, 69120 Heidelberg, Germany); Krijgsveld J ( Genome Biology Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany.); Feuerer M ( Immune Tolerance, Tumor Immunology Program, German Cancer Research Center, 69120 Heidelberg, Germany)
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 ß-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.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	7
Volume Number	195
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2015-10-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Hematopoiesis Immunology Hepatocyte Nuclear Factor 1-alpha Physiology T-lymphocytes, Regulatory Thymus Gland Animals Cell Lineage Cell Proliferation Forkhead Transcription Factors Metabolism Gene Expression Profiling Genetics Mice Mice, Inbred C57bl Mice, Knockout Proteome Signal Transduction Cytology Beta Catenin Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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