title: IL-4 confers NK stimulatory capacity to murine dendritic cells: a signaling pathway involving KARAP/DAP12-triggering receptor expressed on myeloid cell 2 molecules.
abstract: Dendritic cells (DC) regulate NK cell functions, but the signals required for the DC-mediated NK cell activation, i.e., DC-activated NK cell (DAK) activity, remain poorly understood. Upon acute inflammation mimicked by LPS or TNF-alpha, DC undergo a maturation process allowing T and NK cell activation in vitro. Chronic inflammation is controlled in part by Th2 cytokines. In this study, we show that IL-4 selectively confers to DC NK but not T cell stimulatory capacity. IL-4 is mandatory for mouse bone marrow-derived DC grown in GM-CSF (DC(GM/IL-4)) to promote NK cell activation in the draining lymph nodes. IL-4-mediated DAK activity depends on the KARAP/DAP12-triggering receptor expressed on myeloid cell 2 signaling pathway because: 1) gene targeting of the adaptor molecule KARAP/DAP12, a transmembrane polypeptide with an intracytoplasmic immunoreceptor tyrosine-based activation motif, suppresses the DC(GM/IL-4) capacity to activate NK cells, and 2) IL-4-mediated DAK activity is significantly blocked by soluble triggering receptor expressed on myeloid cell 2 Fc molecules. These data outline a novel role for Th2 cytokines in the regulation of innate immune responses through triggering receptors expressed on myeloid cells.
authors.affiliation: ERM0208 Institut National de la Santé et de la Recherche Médicale, Department of Clinical Biology, Institut Gustave Roussy, Villejuif, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Terme
authors.forename: Elena
authors.initials: E
authors.lastname: Tomasello
authors.forename: Koji
authors.initials: K
authors.lastname: Maruyama
authors.forename: Florent
authors.initials: F
authors.lastname: Crépineau
authors.forename: Nathalie
authors.initials: N
authors.lastname: Chaput
authors.forename: Caroline
authors.initials: C
authors.lastname: Flament
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Marolleau
authors.forename: Eric
authors.initials: E
authors.lastname: Angevin
authors.forename: Erwin F
authors.initials: EF
authors.lastname: Wagner
authors.forename: Benoît
authors.initials: B
authors.lastname: Salomon
authors.forename: François A
authors.initials: FA
authors.lastname: Lemonnier
authors.forename: Hiro
authors.initials: H
authors.lastname: Wakasugi
authors.forename: Marco
authors.initials: M
authors.lastname: Colonna
authors.forename: Eric
authors.initials: E
authors.lastname: Vivier
authors.forename: Laurence
authors.initials: L
authors.lastname: Zitvogel
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport / Q000096:biosynthesis / Q000502:physiology*; D019264:Adoptive Transfer; D000818:Animals; D002450:Cell Communication / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D005260:Female; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D015847:Interleukin-4 / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D016513:Mice, SCID; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C498716:Trem2 protein, mouse; D014409:Tumor Necrosis Factor-alpha; C484963:Tyrobp protein, mouse; D015847:Interleukin-4