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Nat Immunol. 2017 Oct;18(10):1160-1172. doi: 10.1038/ni.3799. Epub 2017 Aug 7.

Genome-wide DNA-methylation landscape defines specialization of regulatory T cells in tissues.

Author information

1
Immune Tolerance Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
2
Division of Applied Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
3
Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Heidelberg, Germany.
4
Division of Epigenetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
5
Genomics and Proteomics Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany.
6
Research Group Genome Organization &Function, German Cancer Research Center (DKFZ), Heidelberg, Germany.
7
Heidelberg Center for Personalized Oncology (DKFZ-HIPO), German Cancer Research Center (DKFZ), Heidelberg, Germany.
8
Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
9
Department of Molecular Medicine II, Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany.
10
National Center for Tumor Diseases (NCT), Heidelberg, Germany.
11
German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
12
Institute of Immunology, Regensburg Center for Interventional Immunology (RCI), University Regensburg and University Hospital Regensburg, Regensburg, Germany.

Abstract

Regulatory T cells (Treg cells) perform two distinct functions: they maintain self-tolerance, and they support organ homeostasis by differentiating into specialized tissue Treg cells. We found that epigenetic modifications defined the molecular characteristics of tissue Treg cells. Tagmentation-based whole-genome bisulfite sequencing revealed more than 11,000 regions that were methylated differentially in pairwise comparisons of tissue Treg cell populations and lymphoid T cells. Similarities in the epigenetic landscape led to the identification of a common tissue Treg cell population that was present in many organs and was characterized by gain and loss of DNA methylation that included many gene sites associated with the TH2 subset of helper T cells, such as the gene encoding cytokine IL-33 receptor ST2, as well as the production of tissue-regenerative factors. Furthermore, the ST2-expressing population was dependent on the transcriptional regulator BATF and could be expanded by IL-33. Thus, tissue Treg cells integrate multiple waves of epigenetic reprogramming that define their tissue-restricted specialization.

PMID:
28783152
PMCID:
PMC5912503
DOI:
10.1038/ni.3799
[Indexed for MEDLINE]
Free PMC Article

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