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

gamma delta T cells are major providers of the pro-inflammatory cytokines interferon-gamma (IFN gamma) and interleukin-17 (IL-17)in protective or pathogenic immune responses. Notably, murine gamma delta T cells commit to either IFN gamma 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 gamma delta 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 gamma delta T cell subpopulations, with an emphasis on genome-wide studies and their added value to elucidate the regulation of gamma delta T cell differentiation at the transcriptional and epigenetic (chromatin) levels. (C) 2015 Elsevier Ltd. All rights reserved.