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Blood, 15 March 2008, Vol. 111, No. 6, pp. 3062-3069. Prepublished online as a Blood First Edition Paper on November 9, 2007; DOI 10.1182/blood-2007-02-071910. This Article Full Text (PDF) All Versions of this Article: blood-2007-02-071910v1 111/6/3062    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 Shin, A. Articles by Schnurr, M. Search for Related Content PubMed PubMed Citation Articles by Shin, A. Articles by Schnurr, M. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 2, 2007 Accepted October 21, 2007 P2Y receptor signaling regulates phenotype and IFN- secretion of human plasmacytoid dendritic cells Amanda Shin, Tracey Toy, Simon Rothenfusser, Neil Robson, Julia Vorac, Marc Dauer, Moritz Stuplich, Stefan Endres, Jonathan Cebon, Eugene Maraskovsky*, and Max Schnurr Department of Internal Medicine, University of Munich, Munich, Germany Melbourne Centre for Clinical Sciences, Ludwig Institute for Cancer Research, Heidelberg, Victoria, Australia Division of Clinical Pharmacology, University of Munich, Munich, Germany Research Department, CSL Limited, Parkville, Victoria, Australia * Corresponding author; email: eugene_maraskovsky{at}csl.com.au. Plasmacytoid dendritic cells (PDCs) play powerful regulatory roles in innate and adaptive immune responses and are a major source of type I interferon (IFN) following viral infection. During inflammation and mechanical stress, cells release nucleotides into the extracellular space where they act as signaling molecules via G protein-coupled P2Y receptors. We have previously reported on the regulation of myeloid DC function by nucleotides. Here, we report that human PDCs express several subtypes of P2Y receptors and mobilize intracellular calcium in response to nucleotide exposure. As a functional consequence PDCs acquire a mature phenotype which is further enhanced in the context of CD40-ligation. Strikingly, nucleotides strongly inhibit IFN- secretion induced by influenza virus or CpG-A. This effect is most pronounced for the uridine nucleotides UDP, UTP and the sugar nucleotide UDP-glucose, ligands of P2Y6, P2Y4 and P2Y14, respectively. Nucleotide-induced inhibition of IFN- production is blocked by suramin, a P2Y receptor antagonist. Pharmacological data point towards a role of protein kinase C in the negative regulation of type I IFN. Manipulating PDC function with P2Y receptor agonists may offer novel therapeutic strategies for autoimmune diseases or cancer. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. I. Sesma, C. R. Esther Jr., S. M. Kreda, L. Jones, W. O'Neal, S. Nishihara, R. A. Nicholas, and E. R. Lazarowski Endoplasmic Reticulum/Golgi Nucleotide Sugar Transporters Contribute to the Cellular Release of UDP-sugar Signaling Molecules J. Biol. Chem., May 1, 2009; 284(18): 12572 - 12583. [Abstract] [Full Text] [PDF]

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