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Blood, 15 April 2008, Vol. 111, No. 8, pp. 4245-4253. Prepublished online as a Blood First Edition Paper on February 7, 2008; DOI 10.1182/blood-2007-03-081398. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-03-081398v1 111/8/4245    most recent Alert me when this article is cited Alert me if a correction is posted 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 Meyer-Wentrup, F. Articles by Adema, G. J. Search for Related Content PubMed PubMed Citation Articles by Meyer-Wentrup, F. Articles by Adema, G. J. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 21, 2007 Accepted January 31, 2008 Targeting DCIR on human plasmacytoid dendritic cells results in antigen presentation and inhibits IFN- production Friederike Meyer-Wentrup, Daniel Benitez-Ribas, Paul J. Tacken, Cornelis J.A. Punt, Carl G. Figdor, I. Jolanda M. de Vries, and Gosse J. Adema* Department of Tumor Immunology, Radboud University Nijmegen Medical Centre and Nijmegen Centre for Molecular Life Sciences, Nijmegen, Netherlands Department of Medical Oncology, Radboud University Nijmegen Medical Centre and Nijmegen Centre for Molecular Life Sciences, Nijmegen, Netherlands * Corresponding author; email: g.adema{at}ncmls.ru.nl. C-type lectin receptors (CLRs) fulfill multiple functions within the immune system by recognition of carbohydrate moieties on foreign or (altered) self structures. CLRs on myeloid dendritic cells (DCs) have been well characterized as pattern-recognition receptors (PRRs) combining ligand internalization with complex signaling events. Much less is known about CLR expression and function in human plasmacytoid DCs (pDCs), the major type I IFN producers. In this study, we demonstrate that next to the CLR BDCA-2, human pDCs express DCIR, a CLR with putative immune-inhibitory function, but not dectin-1, mannose receptor or DC-SIGN. DCIR surface levels are reduced upon pDC maturation following TLR9 triggering. Interestingly, DCIR triggering inhibits TLR9-induced IFN- production, while leaving upregulation of co-stimulatory molecule expression unaffected. Furthermore, DCIR is readily internalized into pDCs after receptor triggering. We show that DCIR internalization is clathrin-dependent as it can be inhibited by hypertonic shock and dominant-negative dynamin. Importantly, antigens targeted to pDCs via DCIR are presented to T cells. These findings indicate that targeting DCIR on pDCs not only results in efficient antigen presentation but also affects TLR9-induced IFN- production. Collectively, the data show that targeting of DCIR can modulate human pDC function and may be applied in disease prevention and treatment. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Flores, D. D. Desai, M. Downie, B. Liang, M. P. Reilly, S. E. McKenzie, and R. Clynes Dominant Expression of the Inhibitory Fc{gamma}RIIB Prevents Antigen Presentation by Murine Plasmacytoid Dendritic Cells J. Immunol., December 1, 2009; 183(11): 7129 - 7139. [Abstract] [Full Text] [PDF] F. Angelot, E. Seilles, S. Biichle, Y. Berda, B. Gaugler, J. Plumas, L. Chaperot, F. Dignat-George, P. Tiberghien, P. Saas, et al. 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Benaroch Developmental regulation of MHC II expression and transport in human plasmacytoid-derived dendritic cells Blood, March 5, 2009; 113(10): 2127 - 2135. [Abstract] [Full Text] [PDF] F. Meyer-Wentrup, A. Cambi, B. Joosten, M. W. Looman, I. J. M. de Vries, C. G. Figdor, and G. J. Adema DCIR is endocytosed into human dendritic cells and inhibits TLR8-mediated cytokine production J. Leukoc. Biol., March 1, 2009; 85(3): 518 - 525. [Abstract] [Full Text] [PDF] A. De Filippo, R. J. Binder, C. Camisaschi, V. Beretta, F. Arienti, A. Villa, P. Della Mina, G. Parmiani, L. Rivoltini, and C. Castelli Human Plasmacytoid Dendritic Cells Interact with gp96 via CD91 and Regulate Inflammatory Responses J. Immunol., November 1, 2008; 181(9): 6525 - 6535. [Abstract] [Full Text] [PDF] D. Benitez-Ribas, P. Tacken, C. J. A. Punt, I. J. M. de Vries, and C. G. Figdor Activation of Human Plasmacytoid Dendritic Cells by TLR9 Impairs Fc{gamma}RII-Mediated Uptake of Immune Complexes and Presentation by MHC Class II J. Immunol., October 15, 2008; 181(8): 5219 - 5224. [Abstract] [Full Text] [PDF] A. A. Lambert, C. Gilbert, M. Richard, A. D. Beaulieu, and M. J. Tremblay The C-type lectin surface receptor DCIR acts as a new attachment factor for HIV-1 in dendritic cells and contributes to trans- and cis-infection pathways Blood, August 15, 2008; 112(4): 1299 - 1307. [Abstract] [Full Text] [PDF]

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