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Blood, 15 November 2004, Vol. 104, No. 10, pp. 3267-3275. Prepublished online as a Blood First Edition Paper on July 8, 2004; DOI 10.1182/blood-2004-01-0380. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-01-0380v1 104/10/3267    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Borg, C. Articles by Zitvogel, L. Search for Related Content PubMed PubMed Citation Articles by Borg, C. Articles by Zitvogel, L. Related Collections Immunobiology Phagocytes Cytoskeleton Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY NK cell activation by dendritic cells (DCs) requires the formation of a synapse leading to IL-12 polarization in DCs Christophe Borg, Abdelali Jalil, Diego Laderach, Kouji Maruyama, Hiro Wakasugi, Sabine Charrier, Bernhard Ryffel, Alessandra Cambi, Carl Figdor, William Vainchenker, Anne Galy, Anne Caignard, and Laurence Zitvogel From the ERM0208 Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Clinical Biology, Institut Gustave Roussy, Villejuif, France; U487 INSERM, Institut Gustave Roussy, Villejuif, France; U362 INSERM, Institut Gustave Roussy, Villejuif Généthon, Evry, France; Pharmacology Division, National Cancer Center, Tokyo, Japan; GEM2358, Centre National de la Recherche Scientifique (CNRS), Orleans, France; and University Medical Center, Nijmegen, the Netherlands. Mature dendritic cells (mDCs) can trigger the effector functions of natural killer (NK) cells. Knock-out, small-interfering RNA or neutralizing antibodies targeting interleukin 12 (IL-12) subunits revealed a critical role for IL-12 in NK cell interferon (IFN-) secretion promoted by mDCs. However, NK cell activation by DCs also required direct cell-to-cell contacts. DC-mediated NK cell activation involved the formation of stimulatory synapses between DCs and NK cells. The formation of DC/NK cell conjugates depended on cytoskeleton remodeling and lipid raft mobilization in DCs. Moreover, the disruption of the DC cytoskeleton using pharmacologic agents or the loss-of-function mutation of the Wiskott-Aldrich syndrome protein abolished the DC-mediated NK cell activation. Synapse formation promoted the polarized secretion of preassembled stores of IL-12 by DCs toward the NK cell. The synaptic delivery of IL-12 by DCs was required for IFN- secretion by NK cells, as assessed using inhibitors of cytoskeleton rearrangements and transwell experiments. Therefore, the cross-talk between DCs and NK cells is dictated by functional synapses. (Blood. 2004;104:3267-3275) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: The yin-yang in immunity Bo Dupont Blood 2004 104: 3002-3003. [Full Text] [PDF] This article has been cited by other articles: A. Iannello, O. Debbeche, S. Samarani, and A. Ahmad Antiviral NK cell responses in HIV infection: II. viral strategies for evasion and lessons for immunotherapy and vaccination J. Leukoc. Biol., July 1, 2008; 84(1): 27 - 49. [Abstract] [Full Text] [PDF] T. Strowig, F. Brilot, and C. Munz Noncytotoxic Functions of NK Cells: Direct Pathogen Restriction and Assistance to Adaptive Immunity J. Immunol., June 15, 2008; 180(12): 7785 - 7791. 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