Diversification and functional specialization of human NK cell subsets

Frank Cichocki, Heinrich Schlums, Jakob Theorell, Bianca Tesi, Jeffrey S. Miller, Hans Gustaf Ljunggren, Yenan T. Bryceson

Research output: Contribution to journalArticlepeer-review

48 Scopus citations


Natural killer (NK) cells are lymphocytes that participate in different facets of immunity. They can act as innate sentinels through recognition and eradication of infected or transformed target cells, so-called immunosurveillance. In addition, they can contain immune responses through the killing of other activated immune cells, so-called immunoregulation. Furthermore, they instruct and regulate immune responses by producing pro-inflammatory cytokines such as IFN-γ, either upon direct target cell recognition or by relaying cytokine cues from various cell types. Recent studies in mouse and man have uncovered infection-associated expansions of NK cell subsets with specific receptor repertoires and diverse patterns of intracellular signaling molecule expression. Moreover, distinct attributes of NK cells in tissues, including tissue-resident subsets, are being further elucidated. Findings support an emerging theme of ever-increasing diversification and functional specialization among different NK cell subsets, with a functional dichotomy between subsets involved in immunoregulation or immunosurveillance. The epigenetic landscapes and transcriptional profiles of different NK cell subsets are providing insights into the molecular regulation of effector functions. Here, we review phenotypic, functional, and developmental characteristics of a spectrum of human NK cell subsets. We also discuss the molecular underpinnings of different NK cell subsets and their potential contributions to immunity as well as disease susceptibility.

Original languageEnglish (US)
Pages (from-to)63-93
Number of pages31
JournalCurrent Topics in Microbiology and Immunology
StatePublished - Feb 1 2016

Bibliographical note

Funding Information:
F.C. is an Amy Strelzer Manasevit Research Program Scholar and is supported by a National Marrow Donor Program Award (CON000000052310). Y.T.B. is supported by the European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement No. 311335, Swedish Research Council, Norwegian Research Council, Swedish Foundation for Strategic Research, Wallenberg Foundation, Swedish Cancer Foundation, Swedish Childhood Cancer Foundation, Stockholm County Council (ALF project), and Histiocytosis Society.

Publisher Copyright:
© Springer International Publishing Switzerland 2015.


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