title: NK cell development and function--plasticity and redundancy unleashed.
abstract: Bone marrow-derived natural killer (NK) cells constitute the major subset of cytotoxic lymphocytes in peripheral blood. They provide innate defense against intracellular infection or malignancy and contribute to immune homeostasis. Large numbers of NK cells are also present in tissues, including the liver and uterus, where they can mediate immunosurveillance but also play important roles in tissue remodeling and vascularization. Here, we review the pathways involved in NK cell lineage commitment and differentiation, discussing relationships to other lymphocyte populations and highlighting genetic determinants. Characterizing NK cells from distinct tissues and during infections have revealed subset specializations, reflecting inherent cellular plasticity. In this context, we discuss how different environmental and inflammatory stimuli may shape NK cells. Particular emphasis is placed on genes identified as being critical for NK cell development, differentiation, and function from studies of model organisms or associations with disease. Such studies are also revealing important cellular redundancies. Here, we provide a view of the genetic framework constraining NK cell development and function, pinpointing molecules required for these processes but also underscoring plasticity and redundancy that may underlie robust immunological function. With this view, built in redundancy may highlight the importance of NK cells to immunity.
authors.affiliation: Division of Hematology, Oncology and Transplantation, University of Minnesota Cancer Center, Minneapolis, MN, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Cichocki
authors.affiliation: Lund Research Center for Stem Cell Biology and Cell Therapy, Lund University, Lund, Sweden.
authors.forename: Ewa
authors.initials: E
authors.lastname: Sitnicka
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden; Broegelmann Research Laboratory, Institute 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: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D006801:Humans; D007109:Immunity / Q000502:physiology; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*
keywords: Cytokine production; Cytotoxicity; Natural killer cells; Primary immunodeficiency; Single nucleotide polymorphisms; Transcription factors