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Interleukin-12 bypasses common gamma-chain signalling in emergency natural killer cell lymphopoiesis

Author

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  • Isabel Ohs

    (Inflammation Research, Institute of Experimental Immunology, University of Zurich)

  • Maries van den Broek

    (Tumor Immunology, Institute of Experimental Immunology, University of Zurich)

  • Kathrin Nussbaum

    (Inflammation Research, Institute of Experimental Immunology, University of Zurich)

  • Christian Münz

    (Viral Immunobiology, Institute of Experimental Immunology, University of Zurich)

  • Sebastian J. Arnold

    (Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, and BIOSS Centre of Biological Signalling Studies, Albert-Ludwigs-University
    BIOSS Centre of Biological Signalling Studies, Albert-Ludwigs-University)

  • Sergio A. Quezada

    (Cancer Immunology Unit, University College London Cancer Institute)

  • Sonia Tugues

    (Inflammation Research, Institute of Experimental Immunology, University of Zurich)

  • Burkhard Becher

    (Inflammation Research, Institute of Experimental Immunology, University of Zurich)

Abstract

Differentiation and homeostasis of natural killer (NK) cells relies on common gamma-chain (γc)-dependent cytokines, in particular IL-15. Consequently, NK cells do not develop in mice with targeted γc deletion. Herein we identify an alternative pathway of NK-cell development driven by the proinflammatory cytokine IL-12, which can occur independently of γc-signalling. In response to viral infection or upon exogenous administration, IL-12 is sufficient to elicit the emergence of a population of CD122+CD49b+ cells by targeting NK-cell precursors (NKPs) in the bone marrow (BM). We confirm the NK-cell identity of these cells by transcriptome-wide analyses and their ability to eliminate tumour cells. Rather than using the conventional pathway of NK-cell development, IL-12-driven CD122+CD49b+ cells remain confined to a NK1.1lowNKp46low stage, but differentiate into NK1.1+NKp46+ cells in the presence of γc-cytokines. Our data reveal an IL-12-driven hard-wired pathway of emergency NK-cell lymphopoiesis bypassing steady-state γc-signalling.

Suggested Citation

  • Isabel Ohs & Maries van den Broek & Kathrin Nussbaum & Christian Münz & Sebastian J. Arnold & Sergio A. Quezada & Sonia Tugues & Burkhard Becher, 2016. "Interleukin-12 bypasses common gamma-chain signalling in emergency natural killer cell lymphopoiesis," Nature Communications, Nature, vol. 7(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13708
    DOI: 10.1038/ncomms13708
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