title: Epigenetic and transcriptional signatures of stable versus plastic differentiation of proinflammatory γδ T cell subsets.
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.
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Nina
authors.initials: N
authors.lastname: Schmolka
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Karine
authors.initials: K
authors.lastname: Serre
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Ana R
authors.initials: AR
authors.lastname: Grosso
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.|Blizard Institute, Barts and The London School of Medicine, Queen Mary University of London, UK.
authors.forename: Margarida
authors.initials: M
authors.lastname: Rei
authors.affiliation: Blizard Institute, Barts and The London School of Medicine, Queen Mary University of London, UK.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Pennington
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.|Escola Superior de Tecnologia da Saúde de Lisboa, Lisbon, Portugal.
authors.forename: Anita Q
authors.initials: AQ
authors.lastname: Gomes
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.|Instituto Gulbenkian de Ciência, Oeiras, Portugal.
authors.forename: Bruno
authors.initials: B
authors.lastname: Silva-Santos
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D006657:Histones / Q000378:metabolism; D008745:Methylation; D051379:Mice; D018345:Mice, Knockout; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism; D059467:Transcriptome
chemical_list: D016207:Cytokines; D006657:Histones; D016692:Receptors, Antigen, T-Cell, gamma-delta