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.
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Portugal.
Nina
N
Schmolka
London Research Institute, Cancer Research UK, London, UK; Immunity and Cytotoxic Lymphocytes, Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, Lyon, France.
Mélanie
M
Wencker
London Research Institute, Cancer Research UK, London, UK; Peter Gorer Department of Immunobiology, King's College London, London, UK. Electronic address: Adrian.Hayday@cancer.org.uk.
Adrian C
AC
Hayday
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Portugal; Instituto Gulbenkian de Ciência, Oeiras, Portugal. Electronic address: bssantos@medicina.ulisboa.pt.
Bruno
B
Silva-Santos
D000818:Animals; D002454:Cell Differentiation; D044127:Epigenesis, Genetic; D006801:Humans; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology; D014158:Transcription, Genetic
D016692:Receptors, Antigen, T-Cell, gamma-delta
Pro-inflammatory cytokines; T cell development; γδ T cells