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

Silva-Santos and colleagues use genome-wide characterization of the methylation patterns of histone H3 and analysis of transcription factor expression to identify the regulatory framework of peripheral interferon-γ-producing or interleukin 17–producing γδ T cell subsets. 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.