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

Baron, Udo and Floess, Stefan and Wieczorek, Georg and Baumann, Katrin and Gruetzkau, Andreas and Dong, Jun and Thiel, Andreas and Boeld, Tina J. and Hoffmann, Petra and Edinger, Matthias and Tuerbachova, Ivana and Hamann, Alf and Olek, Sven and Huehn, Jochen (2007) DNA demethylation in the human FOXP3 locus discriminates regulatory T cells from activated FOXP3(+) conventional T cells. EUROPEAN JOURNAL OF IMMUNOLOGY, 37 (9). pp. 2378-2389. ISSN 0014-2980,

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Abstract

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 autoinmumity 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.

Item Type: Article
Uncontrolled Keywords: MULTIPLE-SCLEROSIS PATIENTS; TRANSCRIPTION FACTOR FOXP3; METHYLATION ANALYSIS; PERIPHERAL-BLOOD; EXPRESSION; CANCER; NEUROBLASTOMA; CARCINOMA; IDENTIFICATION; IMMUNOTHERAPY; DNA methylation; epigenetic modifications; Treg marker
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie)
Depositing User: Dr. Gernot Deinzer
Date Deposited: 01 Dec 2020 11:58
Last Modified: 11 Jan 2021 07:34
URI: https://pred.uni-regensburg.de/id/eprint/32274

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