Holmes, TD, Wilson, EB, Black, EVI et al. (5 more authors) (2014) Licensed human natural killer cells aid dendritic cell maturation via TNFSF14/LIGHT. Proceedings of the National Academy of Sciences of the United States of America (PNAS) , 111 (52). E5688-E5696. ISSN 1091-6490
Abstract
Interactions between natural killer (NK) cells and dendritic cells (DC) aid DC maturation and promote T cell responses. Here, we have analysed the response of human NK cells to tumor cells and we identify a pathway by which NK-DC interactions occur. Gene expression profiling of tumor-responsive NK cells identified the very rapid induction of TNFSF14 (also known as LIGHT), a cytokine implicated in the enhancement of anti-tumor responses. TNFSF14 protein expression was induced by three primary mechanisms of NK cell activation, namely via the engagement of CD16, by the synergistic activity of multiple target cell-sensing NK cell activation receptors and by the cytokines IL-2 and IL-15. For anti-tumor responses, TNFSF14 was preferentially produced by the licensed NK cell population, defined by the expression of inhibitory receptors specific for self-MHC class I molecules. In contrast, IL-2 and IL-15 treatment induced TNFSF14 production by both licensed and unlicensed NK cells, reflecting the ability of pro-inflammatory conditions to override the licensing mechanism. Importantly, both tumor and cytokine activated NK cells induced DC maturation in a TNFSF14-dependent manner. The coupling of TNFSF14 production to tumor-sensing NK cell activation receptors links the tumor immune surveillance function of NK cells to DC maturation and adaptive immunity. Furthermore, regulation by NK cell licensing helps to safeguard against TNFSF14 production in response to healthy tissues.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | (c) 2014, PNAS. Freely available online through the PNAS open access option. In order to comply with the publisher requirements the University does not require the author to sign a non-exclusive licence for this paper. |
Keywords: | natural killer cells; NK–DC interactions; TNFSF14; NK-cell licensing; tumor immunity |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > Institute of Molecular Medicine (LIMM) (Leeds) > Section of Oncology and Clinical Research (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 06 May 2015 09:21 |
Last Modified: | 16 Jan 2018 05:53 |
Published Version: | http://dx.doi.org/10.1073/pnas.1411072112 |
Status: | Published |
Publisher: | National Academy of Sciences |
Identification Number: | 10.1073/pnas.1411072112 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:85696 |