Journal
SEMINARS IN IMMUNOLOGY
Volume 26, Issue 2, Pages 114-126Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.smim.2014.02.003
Keywords
Natural killer cells; Primary immunodeficiency; Single nucleotide polymorphisms; Transcription factors; Cytotoxicity; Cytokine production
Categories
Funding
- European Research Council under the European Union's Seventh Framework Programme [FP/2007-2013]
- ERC Grant [311335]
- Swedish Research Council
- Swedish Foundation for Strategic Research
- Swedish Cancer Foundation
- Swedish Children's Cancer Foundation
- Histiocytosis Association
- Jeansson's Foundation
- Karolinska Institute Research Foundation
- AFA Forsakring
- Gunnar Nilsson Cancer Foundation
- ALF Clinical Research Award from Lund University Hospital
- Hemato-Linne and Stem Therapy Lund University Programmes
- University of Minnesota T32 Hematology Training Grant
- European Research Council (ERC) [311335] Funding Source: European Research Council (ERC)
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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. (c) 2014 Elsevier Ltd. All rights reserved.
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