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IL-4 and IL-13 modulate natural killer cell responses under inflammatory conditions

David E Ohayon, Durga Krishnamurthy, Michael Brusilovsky and Stephen N Waggoner
J Immunol May 1, 2017, 198 (1 Supplement) 194.11;
David E Ohayon
1Cincinnati Children’s Hosp. Med. Ctr.
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Durga Krishnamurthy
1Cincinnati Children’s Hosp. Med. Ctr.
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Michael Brusilovsky
1Cincinnati Children’s Hosp. Med. Ctr.
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Stephen N Waggoner
1Cincinnati Children’s Hosp. Med. Ctr.
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Abstract

Natural killer (NK) cells are critical producers of IFN-g and mediators of cytotoxicity in response to type 1 inflammatory cytokine (e.g. IL-12) rich environments. Conventional thinking therefore holds that type 2 cytokines (e.g. IL-4 and IL-13) that counter production of IL-12 would inhibit NK cell effector functions and thereby limit the antiviral role of NK cells. In contrast, IL-4 unexpectedly synergized with IL-12 to enhance IFN-g production by mouse NK cells. We now extend this observation to human NK cells, where we find that stimulation with either IL-4 or IL-13 resulted in dose-dependent enhancement of IFN-g and TNF-a expression in response to IL-12. Neither IL-4 nor IL-13 stimulated IFN-g release in the absence of IL-12, suggesting that these type 2 cytokines modulate IL-12 signaling or NK cell responsiveness to IL-12. In contrast to the effect of IL-4 on IL-12 responsiveness, IL-4 (but not IL-13) markedly reduced the expression of IFN-g and TNF-a by human NK cells following engagement of the natural cytotoxicity receptor, NKp46. Likewise, IL-4-treated NK cells demonstrated reduced cytotoxicity towards K562 cells. Our results reveal that IL-4 and IL-13 modulate NK cells in a complex manner, enhancing responsiveness to inflammatory cytokines like IL-12 while diminishing activation via natural cytotoxicity receptors. We speculate that this could have important consequences for NK cell lysis of eosinophils, IFN-g-mediated airway hyperresponsiveness, and other features of allergic or asthmatic diseases associated with aberrant type 2 cytokine production.

  • Copyright © 2017 by The American Association of Immunologists, Inc.
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The Journal of Immunology
Vol. 198, Issue 1 Supplement
1 May 2017
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IL-4 and IL-13 modulate natural killer cell responses under inflammatory conditions
David E Ohayon, Durga Krishnamurthy, Michael Brusilovsky, Stephen N Waggoner
The Journal of Immunology May 1, 2017, 198 (1 Supplement) 194.11;

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IL-4 and IL-13 modulate natural killer cell responses under inflammatory conditions
David E Ohayon, Durga Krishnamurthy, Michael Brusilovsky, Stephen N Waggoner
The Journal of Immunology May 1, 2017, 198 (1 Supplement) 194.11;
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Print ISSN 0022-1767        Online ISSN 1550-6606