title: SHP-1-mediated inhibitory signals promote responsiveness and anti-tumour functions of natural killer cells.
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.
authors.affiliation: 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.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Viant
authors.affiliation: 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.
authors.forename: Aurore
authors.initials: A
authors.lastname: Fenis
authors.affiliation: INSERM, U1048 and Université Toulouse III, Institut de Maladies Métaboliques et Cardiovasculaires, CHU-Rangueil, F-31300 Toulouse, France.
authors.forename: Gaëtan
authors.initials: G
authors.lastname: Chicanne
authors.affiliation: INSERM, U1048 and Université Toulouse III, Institut de Maladies Métaboliques et Cardiovasculaires, CHU-Rangueil, F-31300 Toulouse, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Payrastre
authors.affiliation: 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.
authors.forename: Sophie
authors.initials: S
authors.lastname: Ugolini
authors.affiliation: 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.
authors.forename: Eric
authors.initials: E
authors.lastname: Vivier
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D007694:Killer Cells, Natural / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D055650:NK Cell Lectin-Like Receptor Subfamily A / Q000378:metabolism; D010641:Phenotype; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000378:metabolism*
chemical_list: D015395:Histocompatibility Antigens Class I; D055650:NK Cell Lectin-Like Receptor Subfamily A; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; C509248:Ptpn6 protein, mouse