Epigenetic and transcriptional regulation of γδ T cell differentiation: Programming cells for responses in time and space

γδ T cells are major providers of the pro-inflammatory cytokines interferon-γ (IFNγ) and interleukin-17 (IL-17) in protective or pathogenic immune responses. Notably, murine γδ T cells commit to either IFNγ or IL-17 production during development in the thymus, before any subsequent activation in the periphery. Here we discuss the molecular networks that underlie thymic γδ T cell differentiation, as well as the mechanisms that sustain or modify their functional properties in the periphery. We concentrate on recent findings on lymphoid and tissue-resident γδ T cell subpopulations, with an emphasis on genome-wide studies and their added value to elucidate the regulation of γδ T cell differentiation at the transcriptional and epigenetic (chromatin) levels.