DNA demethylation in the human FOXP3 locus discriminates regulatory T cells from activated FOXP3+ conventional T cells

作者：Udo Baron, Stefan Floess, Georg Wieczorek, Katrin Baumann, Andreas Grützkau, Jun Dong, Andreas Thiel, Tina J. Boeld, Petra Hoffmann, Matthias Edinger, Ivana Türbachova, Alf Hamann, Sven Olek, Jochen Huehn · 发表于：European Journal of Immunology · 年份：2007 · DOI：10.1002/eji.200737594 · 被引用次数：685 · 研究领域：Immune Cell Function and Interaction、T-cell and B-cell Immunology、Cytomegalovirus and herpesvirus research

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.