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NK cell detachment from target cells is regulated by successful cytotoxicity and influences cytokine production

Cellular & Molecular Immunology volume 17, pages 347–355 (2020)Cite this article

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Abstract

Natural killer (NK) cells participate in early immune defenses against pathogens and tumors and play a major role as immune effector and regulatory cells. The NK cell-mediated elimination of an infected or cancerous cell is a highly regulated process that requires the formation of a cell contact, the establishment of an immunological synapse and the polarization and release of lytic granules. Additionally, the detachment of NK cells from target cells is important for NK cells to bind and kill other cells in a process called serial killing. However, very little is known about this detachment process. Here, we show that NK detachment is directly connected to the successful killing of a target cell. The inhibition of killing due to reduced NK cell cytotoxicity or increased target cell resistance results in defective detachment and prolonged contact times. This effect leads to sustained Ca2+ flux in NK cells and the hypersecretion of proinflammatory cytokines. Linking defective cytotoxicity with enhanced cytokine secretion via reduced detachment may explain inflammatory pathologies in several diseases.

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Acknowledgements

We thank Clarissa Liesche for the serpinB9 cDNA and all members of our lab for their help and discussions.

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Author notes

  1. These authors contributed equally: Moritz Anft, Petra Netter

Authors and Affiliations

  1. IfADo-Leibniz Research Centre for Working Environment and Human Factors, Technical University Dortmund, Dortmund, Germany

    Moritz Anft, Petra Netter, Doris Urlaub, Isabel Prager, Samantha Schaffner & Carsten Watzl

  2. University of British Columbia, Vancouver, BC, Canada

    Samantha Schaffner

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  1. Moritz Anft
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Contributions

M.A., P.N., D.U., I.P. and S.S. performed the experiments; M.A., P.N. and C.W. planned the experiments and analyzed the data; and M.A. and C.W. wrote the manuscript.

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Correspondence to Carsten Watzl.

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Anft, M., Netter, P., Urlaub, D. et al. NK cell detachment from target cells is regulated by successful cytotoxicity and influences cytokine production. Cell Mol Immunol 17, 347–355 (2020). https://doi.org/10.1038/s41423-019-0277-2

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