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Nat Immunol. 2013 Oct;14(10):1093-1100. doi: 10.1038/ni.2702. Epub 2013 Sep 1.

Epigenetic and transcriptional signatures of stable versus plastic differentiation of proinflammatory γδ T cell subsets.

Author information

1
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
2
Blizard Institute, Barts and The London School of Medicine, Queen Mary University of London, UK.
3
Escola Superior de Tecnologia da Saúde de Lisboa, Lisbon, Portugal.
4
Instituto Gulbenkian de Ciência, Oeiras, Portugal.
#
Contributed equally

Abstract

Two distinct subsets of γδ T cells that produce interleukin 17 (IL-17) (CD27(-) γδ T cells) or interferon-γ (IFN-γ) (CD27(+) γδ T cells) develop in the mouse thymus, but the molecular determinants of their functional potential in the periphery remain unknown. Here we conducted a genome-wide characterization of the methylation patterns of histone H3, along with analysis of mRNA encoding transcription factors, to identify the regulatory networks of peripheral IFN-γ-producing or IL-17-producing γδ T cell subsets in vivo. We found that CD27(+) γδ T cells were committed to the expression of Ifng but not Il17, whereas CD27(-) γδ T cells displayed permissive chromatin configurations at loci encoding both cytokines and their regulatory transcription factors and differentiated into cells that produced both IL-17 and IFN-γ in a tumor microenvironment.

PMID:
23995235
PMCID:
PMC4834994
DOI:
10.1038/ni.2702
[Indexed for MEDLINE]
Free PMC Article
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