title: Epigenetic Regulation of Adaptive NK Cell Diversification.
abstract: Natural killer (NK) cells were previously considered to represent short-lived, innate lymphocytes. However, mouse models have revealed expansion and persistence of differentiated NK cell subsets in response to cytomegalovirus (CMV) infection, paralleling antigen-specific T cell differentiation. Congruently, analyses of humans have uncovered CMV-associated NK cell subsets characterized by epigenetic diversification processes that lead to altered target cell specificities and functional capacities. Here, focusing on responses to viruses, we review similarities and differences between mouse and human adaptive NK cells, identifying molecular analogies that may be key to transcriptional reprogramming and functional alterations. We discuss possible molecular mechanisms underlying epigenetic diversification and hypothesize that processes driving epigenetic diversification may represent a more widespread mechanism for fine-tuning and optimization of cellular immunity.
authors.affiliation: Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden; Clinical Genetics Unit, Department of Molecular Medicine and Surgery, and Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden.
authors.forename: Bianca
authors.initials: B
authors.lastname: Tesi
authors.affiliation: Centre for Hematology and Regenerative Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Heinrich
authors.initials: H
authors.lastname: Schlums
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Cichocki
authors.affiliation: Centre for Hematology and Regenerative Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden; Broegelmann Research Laboratory, Department of Clinical Sciences, University of Bergen, Bergen, Norway. Electronic address: Yenan.Bryceson@ki.se.
authors.forename: Yenan T
authors.initials: YT
authors.lastname: Bryceson
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics; D000818:Animals; D044822:Biodiversity; D002454:Cell Differentiation; D065150:Cellular Reprogramming; D060966:Clonal Selection, Antigen-Mediated; D003586:Cytomegalovirus Infections / Q000276:immunology*; D044127:Epigenesis, Genetic; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology
keywords: NK cells; adaptive immunity; cellular diversification; epigenetic regulation; infection