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Nat Commun. 2014 Oct 30;5:5108. doi: 10.1038/ncomms6108.

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

Author information

1
1] Centre d'Immunologie de Marseille-Luminy, Aix-Marseille University UM2, Parc Scientifique et Technologique de Luminy, Case 906, 13288 Marseille, France [2] Inserm U1104, 13288 Marseille, France [3] CNRS UMR7280, 13288 Marseille, France.
2
INSERM, U1048 and Université Toulouse III, Institut de Maladies Métaboliques et Cardiovasculaires, CHU-Rangueil, F-31300 Toulouse, France.
3
1] Centre d'Immunologie de Marseille-Luminy, Aix-Marseille University UM2, Parc Scientifique et Technologique de Luminy, Case 906, 13288 Marseille, France [2] Inserm U1104, 13288 Marseille, France [3] CNRS UMR7280, 13288 Marseille, France [4] Service d'Immunologie, Assistance Publique-Hôpitaux de Marseille, Hôpital de la Conception, 13385 Marseille, France.

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 Ca(2+) 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.

PMID:
25355530
DOI:
10.1038/ncomms6108
[Indexed for MEDLINE]

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