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

Authors
  • Delacher, Michael1
  • Imbusch, Charles D2
  • Weichenhan, Dieter3
  • Breiling, Achim4
  • Hotz-Wagenblatt, Agnes5
  • Träger, Ulrike1
  • Hofer, Ann-Cathrin1
  • Kägebein, Danny1
  • Wang, Qi2
  • Frauhammer, Felix2
  • Mallm, Jan-Philipp6, 7
  • Bauer, Katharina7
  • Herrmann, Carl8
  • Lang, Philipp A9
  • Brors, Benedikt2, 10, 11
  • Plass, Christoph3
  • Feuerer, Markus1, 12
  • 1 Immune Tolerance Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. , (Germany)
  • 2 Division of Applied Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany. , (Germany)
  • 3 Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Heidelberg, Germany. , (Germany)
  • 4 Division of Epigenetics, German Cancer Research Center (DKFZ), Heidelberg, Germany. , (Germany)
  • 5 Genomics and Proteomics Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany. , (Germany)
  • 6 Research Group Genome Organization &Function, German Cancer Research Center (DKFZ), Heidelberg, Germany. , (Germany)
  • 7 Heidelberg Center for Personalized Oncology (DKFZ-HIPO), German Cancer Research Center (DKFZ), Heidelberg, Germany. , (Germany)
  • 8 Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany. , (Germany)
  • 9 Department of Molecular Medicine II, Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany. , (Germany)
  • 10 National Center for Tumor Diseases (NCT), Heidelberg, Germany. , (Germany)
  • 11 German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. , (Germany)
  • 12 Institute of Immunology, Regensburg Center for Interventional Immunology (RCI), University Regensburg and University Hospital Regensburg, Regensburg, Germany. , (Germany)
Type
Published Article
Journal
Nature Immunology
Publisher
Springer Nature
Publication Date
Oct 01, 2017
Volume
18
Issue
10
Pages
1160–1172
Identifiers
DOI: 10.1038/ni.3799
PMID: 28783152
Source
Medline
License
Unknown

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.

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