DNA demethylation in the humanFOXP3 locus discriminates regulatory T cells from activated FOXP3+ conventional T cells
| Autor: | Andreas Grützkau, Petra Hoffmann, Alf Hamann, Tina J. Boeld, Jun Dong, Jochen Huehn, Matthias Edinger, Udo Baron, Stefan Floess, Sven Olek, Andreas Thiel, Ivana Türbachova, Georg Wieczorek, Katrin Baumann |
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| Rok vydání: | 2007 |
| Předmět: |
Genetic Markers
Male T-Lymphocytes Immunology chemical and pharmacologic phenomena Biology Lymphocyte Activation medicine.disease_cause Sensitivity and Specificity Autoimmunity Transforming Growth Factor beta medicine Humans Immunology and Allergy Epigenetics Transcription factor Gene Cells Cultured Cell Proliferation Gene Expression Profiling Calcium-Binding Proteins Interleukin-2 Receptor alpha Subunit FOXP3 Forkhead Transcription Factors hemic and immune systems DNA Methylation Molecular biology Immunity Innate Cell biology Gene expression profiling DNA demethylation DNA methylation Trans-Activators Female |
| Zdroj: | European Journal of Immunology. 37:2378-2389 |
| ISSN: | 1521-4141 0014-2980 |
| DOI: | 10.1002/eji.200737594 |
| Popis: | The transcription factor FOXP3 is critical for development and function of regulatory T cells (Treg). Their number and functioning appears to be crucial in the prevention of autoimmunity and allergy, but also to be a negative prognostic marker for various solid tumors. Although expression of the transcription factor FOXP3 currently constitutes the best-known marker for Treg, in humans, transient expression is also observed in activated non-Treg. Extending our recent findings for the murine foxp3 locus, we observed epigenetic modification of several regions in the human FOXP3 locus exclusively occurring in Treg. Importantly, activated conventional CD4(+) T cells and TGF-beta-treated cells displayed no FOXP3 DNA demethylation despite expression of FOXP3, whereas subsets of Treg stable even upon extended in vitro expansion remained demethylated. To investigate whether a whole set of genes might be epigenetically imprinted in the Treg lineage, we conducted a genome-wide differential methylation hybridization analysis. Several genes were found displaying differential methylation between Treg and conventional T cells, but none beside FOXP3 turned out to be entirely specific to Treg when tested on a broad panel of cells and tissues. We conclude that FOXP3 DNA demethylation constitutes the most reliable criterion for natural Treg available at present. |
| Databáze: | OpenAIRE |
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