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IL-15 Promotes Polyfunctional NK Cell Responses to Influenza by Boosting IL-12 Production

Wagstaffe, HR; Nielsen, CM; Riley, EM; Goodier, MR; (2018) IL-15 Promotes Polyfunctional NK Cell Responses to Influenza by Boosting IL-12 Production. The Journal of Immunology , 200 (8) pp. 2738-2747. 10.4049/jimmunol.1701614. Green open access

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Abstract

IL-15 is a key regulator of NK cell maintenance and proliferation and synergizes with other myeloid cell–derived cytokines to enhance NK cell effector function. At low concentrations, trans-presentation of IL-15 by dendritic cells can activate NK cells, whereas at higher concentrations it can act directly on NK cells, independently of accessory cells. In this study, we investigate the potential for IL-15 to boost responses to influenza virus by promoting accessory cell function. We find that coculture of human PBMCs with inactivated whole influenza virus (A/Victoria/361/2011) in the presence of very low concentrations of IL-15 results in increased production of myeloid cell–derived cytokines, including IL-12, IFN-α2, GM-CSF, and IL-1β, and an increased frequency of polyfunctional NK cells (defined by the expression of two or more of CD107a, IFN-γ, and CD25). Neutralization experiments demonstrate that IL-15–mediated enhancement of NK cell responses is primarily dependent on IL-12 and partially dependent on IFN-αβR1 signaling. Critically, IL-15 boosted the production of IL-12 in influenza-stimulated blood myeloid dendritic cells. IL-15 costimulation also restored the ability of less-differentiated NK cells from human CMV-seropositive individuals to respond to influenza virus. These data suggest that very low concentrations of IL-15 play an important role in boosting accessory cell function to support NK cell effector functions.

Type: Article
Title: IL-15 Promotes Polyfunctional NK Cell Responses to Influenza by Boosting IL-12 Production
Open access status: An open access version is available from UCL Discovery
DOI: 10.4049/jimmunol.1701614
Publisher version: https://doi.org/10.4049/jimmunol.1701614
Language: English
Additional information: This article is distributed under the terms of the CC BY 4.0 Unported license. https://creativecommons.org/licenses/by/4.0/
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10080721
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