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Blood, 15 April 2006, Vol. 107, No. 8, pp. 3229-3234. Prepublished online as a Blood First Edition Paper on December 20, 2005; DOI 10.1182/blood-2005-07-2650. This Article Full Text (PDF) Erratum (v107,p3831) All Versions of this Article: 2005-07-2650v1 107/8/3229    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 Savarese, E. Articles by Krug, A. Search for Related Content PubMed PubMed Citation Articles by Savarese, E. Articles by Krug, A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 8, 2005 Accepted November 30, 2005 U1 small nuclear ribonucleoprotein immune complexes induce type I interferon in plasmacytoid dendritic cells via TLR7 Emina Savarese, Ohk-wha Chae, Simon Trowitzsch, Gert Weber, Berthold Kastner, Shizuo Akira, Hermann Wagner, Roland M Schmid, Stefan Bauer, and Anne Krug* Department of Internal Medicine, Technical University Munich, Munich, Germany Department of Cellular Biochemistry, Max Planck Institute for Biophysical Chemistry, Gottingen, Germany Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan Institute of Microbiology and Immunology, Technical University Munich, Munich, Germany * Corresponding author; email: Anne.Krug{at}lrz.tu-muenchen.de. Plasmacytoid dendritic cells (PDC), which produce IFN- in response to autoimmune complexes containing nuclear antigens are thought to be critically involved in the pathogenesis of systemic lupus erythematodes (SLE). One of the immunostimulatory components of SLE-IC is self-DNA, which is recognized through TLR9 in PDC and B cells. Small nuclear ribonucleoproteins (snRNP) are another major component of SLE immune complexes in 30 to 40 % of patients. In this study we show that murine PDC are activated by purifed U1snRNP/anti-Sm immune complexes to produce IFN- and proinflammatory cytokines as well as upregulate costimulatory molecules. The induction of IFN- and IL-6 by U1snRNP in murine bone marrow derived PDC required the presence of intact U1RNA and was largely dependent on TLR7 but independent of TLR3. Intracellularly delivered isolated U1snRNA and oligoribonucleotides derived from the stem loop regions and the Sm binding site of U1snRNA efficiently induced IFN- and IL-6 in FL-DC in a TLR7-dependent manner. The U1snRNA component of U1snRNP immune complexes which are found in SLE patients acts as an endogenous "self" ligand for TLR7, triggering IFN- and IL-6 production in PDC. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Ding, Y. Cai, J. Marroquin, S. T. Ildstad, and J. Yan Plasmacytoid Dendritic Cells Regulate Autoreactive B Cell Activation via Soluble Factors and in a Cell-to-Cell Contact Manner J. Immunol., December 1, 2009; 183(11): 7140 - 7149. [Abstract] [Full Text] [PDF] H. Hagele, R. Allam, R. D. Pawar, and H.-J. Anders Double-stranded RNA activates type I interferon secretion in glomerular endothelial cells via retinoic acid-inducible gene (RIG)-1 Nephrol. Dial. 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