title: NK-dependent DC maturation is mediated by TNFalpha and IFNgamma released upon engagement of the NKp30 triggering receptor.
abstract: Natural killer (NK) cells were recently shown to play a relevant role in the process of dendritic cell (DC) maturation. This function is exerted either by direct DC stimulation or through killing those DCs that did not properly acquire a mature phenotype. While killing of immature DCs is dependent on the function of the NKp30 triggering receptor, the mechanism by which NK cells induce DC maturation is still unclear. In this study, we show that also the NK-mediated induction of DC maturation is dependent on NKp30. Upon NK/DC interaction, resulting in NKp30 engagement, NK cells produced tumor necrosis factor alpha (TNFalpha) (and interferon gamma [IFNgamma]) that, in turn, promoted DC maturation. Masking of NKp30 with specific monoclonal antibodies (mAbs) strongly reduced maturation of DCs cocultured with NK cells. In addition, supernatant from NK cells stimulated via NKp30 induced DC maturation, and this effect was neutralized by anti-TNFalpha antibodies (Abs). This NKp30 function is controlled by the HLA-specific inhibitory NK receptors. Accordingly, the ability to promote maturation was essentially confined to NK cells expressing the killer immunoglobulin-like receptor-negative (KIR-) NKG2A(dull) phenotype. Finally, the analysis of perforin-deficient NK cells allowed the dissection of the 2 NKp30-mediated NK-cell functions, since NKp30 could induce cytokine-dependent DC maturation in the absence of NK-mediated DC killing.
authors.affiliation: Istituto Scientifico per la Ricerca sul Cancro (IST), Genova, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Vitale
authors.forename: Mariella
authors.initials: M
authors.lastname: Della Chiesa
authors.forename: Simona
authors.initials: S
authors.lastname: Carlomagno
authors.forename: Daniela
authors.initials: D
authors.lastname: Pende
authors.forename: Maurizio
authors.initials: M
authors.lastname: Aricò
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moretta
authors.forename: Alessandro
authors.initials: A
authors.lastname: Moretta
mesh_terms: D002454:Cell Differentiation; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology*; D015616:Histiocytosis, Non-Langerhans-Cell / Q000276:immunology / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000378:metabolism*; D055628:Natural Cytotoxicity Triggering Receptor 3; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D011971:Receptors, Immunologic / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D015395:Histocompatibility Antigens Class I; D008562:Membrane Glycoproteins; C431710:NCR3 protein, human; D055628:Natural Cytotoxicity Triggering Receptor 3; D052899:Pore Forming Cytotoxic Proteins; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha; D054353:Perforin; D007371:Interferon-gamma