Abstract
Natural killer (NK) cells deliver cytotoxic granules and immunomodulatory cytokines in response to transformed and virally infected cells. NK cell functions are under the control of a large number of germline-encoded receptors that recognize various ligands on target cells, but NK cells also respond to cytokines in the surrounding environment. The interaction between NK cell receptors and their ligands delivers either inhibitory or activating signals. The cytokine milieu further shapes NK cell responses, either directly or by influencing the way inhibitory or activating signals are perceived by NK cells. In this review, we discuss how NK cell function is controlled by inhibitory receptors and MHC-I molecules, how activating receptors contribute to NK cell education, and finally, how cytokines secreted by the surrounding cells affect NK cell responsiveness. Inputs at these three levels involve different cell types and are seamlessly integrated to form a functional NK cell population.
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- NK:
-
Natural killer
- MHC-I:
-
MHC class I
- CLP:
-
Common lymphoid precursor
- KIR:
-
Killer inhibitory receptors
- ITIM:
-
Immunoreceptor tyrosine-based inhibitory motifs
- LIR:
-
Leukocyte immunoglobulin-like receptor
- SHP:
-
SH2 domain phosphatase
- SHIP:
-
SH2 domain-containing inositol 5-phosphatase
- TAP:
-
Transporter associated with antigen processing
- β2m:
-
Β2-microglobulin
- NCR:
-
Natural cytotoxicity receptor
- RAG:
-
Recombinase-activating gene
- IFN-γ:
-
Interferon-γ
- LFA-1:
-
Leukocyte function-associated antigen 1
- DC:
-
Dendritic cell
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Acknowledgments
The authors thank all the members of the Höglund and Kärre laboratories for their support and for the helpful discussions, and we apologize to the many contributors to this field whose work could not been reviewed or cited due to space constraints. Our work is supported by grants from Karolinska Institutet to PH, MHJ, and KK; from the Åke Wiberg foundation, Magnus Bergwall foundation, the Royal Swedish Academy of Sciences, Syskonen Svensson foundation and the Swedish National Board of Health and Welfare to MHJ; from the Stockholm City Council (IMTAC thematic center to PH MJH and KK and ALF grant to PH); from the Ragnar Söderberg Foundation to PH; and from the Swedish Foundation for Strategic Research, the Swedish Research Council, and the Swedish Cancer Society to KK and PH. AKW, SW and SG are supported by individual KID grants from Karolinska Institutet. NK was supported by an IMTAC grant.
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Kadri, N. et al. (2015). Dynamic Regulation of NK Cell Responsiveness. In: Vivier, E., Di Santo, J., Moretta, A. (eds) Natural Killer Cells. Current Topics in Microbiology and Immunology, vol 395. Springer, Cham. https://doi.org/10.1007/82_2015_485
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