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SHP-1-mediated inhibitory signals promote responsiveness and anti-tumour functions of natural killer cells

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  • Charlotte Viant

    (Centre d’Immunologie de Marseille-Luminy, Aix-Marseille University UM2, Parc Scientifique et Technologique de Luminy, Case 906
    Inserm U1104
    CNRS UMR7280)

  • Aurore Fenis

    (Centre d’Immunologie de Marseille-Luminy, Aix-Marseille University UM2, Parc Scientifique et Technologique de Luminy, Case 906
    Inserm U1104
    CNRS UMR7280)

  • Gaëtan Chicanne

    (INSERM, U1048 and Université Toulouse III, Institut de Maladies Métaboliques et Cardiovasculaires, CHU-Rangueil)

  • Bernard Payrastre

    (INSERM, U1048 and Université Toulouse III, Institut de Maladies Métaboliques et Cardiovasculaires, CHU-Rangueil)

  • Sophie Ugolini

    (Centre d’Immunologie de Marseille-Luminy, Aix-Marseille University UM2, Parc Scientifique et Technologique de Luminy, Case 906
    Inserm U1104
    CNRS UMR7280)

  • Eric Vivier

    (Centre d’Immunologie de Marseille-Luminy, Aix-Marseille University UM2, Parc Scientifique et Technologique de Luminy, Case 906
    Inserm U1104
    CNRS UMR7280
    Service d’Immunologie, Assistance Publique—Hôpitaux de Marseille, Hôpital de la Conception)

Abstract

Natural killer (NK) cells are cytotoxic innate lymphoid cells that are involved in immune defense. NK cell reactivity is controlled in part by MHC class I recognition by inhibitory receptors, but the underlying molecular mechanisms remain undefined. Using a mouse model of conditional deletion in NK cells, we show here that the protein tyrosine phosphatase SHP-1 is essential for the inhibitory function of NK cell MHC class I receptors. In the absence of SHP-1, NK cells are hyporesponsive to tumour cells in vitro and their early Ca2+ signals are compromised. Mice without SHP-1 in NK cells are unable to reject MHC class I-deficient transplants and to control tumours in vivo. Thus, the inhibitory activity of SHP-1 is needed for setting the threshold of NK cell reactivity.

Suggested Citation

  • Charlotte Viant & Aurore Fenis & Gaëtan Chicanne & Bernard Payrastre & Sophie Ugolini & Eric Vivier, 2014. "SHP-1-mediated inhibitory signals promote responsiveness and anti-tumour functions of natural killer cells," Nature Communications, Nature, vol. 5(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6108
    DOI: 10.1038/ncomms6108
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