Schmolka, NinaSerre, KarineGrosso, Ana R.Rei, MargaridaPennington, Daniel J.Gomes, Anita Q.Silva-Santos, Bruno2014-08-262014-08-262013-09Schmolka N, Serre K, Grosso AR, Rei M, Pennington DJ, Gomes AQ, Silva-Santos B. Epigenetic and transcriptional signatures of stable versus plastic differentiation of proinflammatory γδ T cell subsets. Nat Immunol. 2013;14(10):1093-100.http://hdl.handle.net/10400.21/3768Two 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.engCell differentiationCytokinesGene expression profilingGene expression regulationMethylationT-Lymphocyte subsetsTh1 cellsTh17 cellsTranscriptomejournal article10.1038/ni.2702