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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 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 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 Savarese, E. Articles by Krug, A. Search for Related Content PubMed PubMed Citation Articles by Savarese, E. Articles by Krug, A. Related Collections Signal Transduction Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY U1 small nuclear ribonucleoprotein immune complexes induce type I interferon in plasmacytoid dendritic cells through TLR7 Emina Savarese, Ohk-wha Chae, Simon Trowitzsch, Gert Weber, Berthold Kastner, Shizuo Akira, Hermann Wagner, Roland M. Schmid, Stefan Bauer, and Anne Krug From the Department of Internal Medicine, Technical University Munich, Germany; Institute of Microbiology and Immunology, Technical University Munich, Germany; Department of Cellular Biochemistry, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany; and Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Japan. Plasmacytoid dendritic cells (PDCs), which produce IFN- in response to autoimmune complexes containing nuclear antigens, are thought to be critically involved in the pathogenesis of systemic lupus erythematosus (SLE). One of the immunostimulatory components of SLE immune complexes (SLE-ICs) is self DNA, which is recognized through Tlr9 in PDCs and B cells. Small nuclear ribonucleoproteins (snRNPs) are another major component of SLE-ICs in 30% to 40% of patients. In this study, we show that murine PDCs are activated by purified U1snRNP/anti-Sm ICs to produce IFN- and proinflammatory cytokines and to up-regulate costimulatory molecules. The induction of IFN- and IL-6 by U1snRNPs in murine bone marrow–derived PDCs 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 Flt3L-cultured DCs in a Tlr7-dependent manner. The U1snRNA component of U1snRNP immune complexes, found in patients with SLE, acts as an endogenous "self" ligand for Tlr7 and triggers IFN- and IL-6 production in PDCs. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. Yasuda, C. Richez, J. W. Maciaszek, N. Agrawal, S. Akira, A. Marshak-Rothstein, and I. R. Rifkin Murine Dendritic Cell Type I IFN Production Induced by Human IgG-RNA Immune Complexes Is IFN Regulatory Factor (IRF)5 and IRF7 Dependent and Is Required for IL-6 Production J. Immunol., June 1, 2007; 178(11): 6876 - 6885. [Abstract] [Full Text] [PDF] R. D. Pawar, A. Ramanjaneyulu, O. P. Kulkarni, M. Lech, S. Segerer, and H.-J. Anders Inhibition of Toll-Like Receptor-7 (TLR-7) or TLR-7 plus TLR-9 Attenuates Glomerulonephritis and Lung Injury in Experimental Lupus J. Am. Soc. Nephrol., June 1, 2007; 18(6): 1721 - 1731. [Abstract] [Full Text] [PDF] M. Severa, M. E. Remoli, E. Giacomini, V. Annibali, V. Gafa, R. Lande, M. Tomai, M. Salvetti, and E. M. Coccia Sensitization to TLR7 Agonist in IFN-beta-Preactivated Dendritic Cells J. Immunol., May 15, 2007; 178(10): 6208 - 6216. [Abstract] [Full Text] [PDF] C. Bourquin, L. Schmidt, V. Hornung, C. Wurzenberger, D. Anz, N. Sandholzer, S. Schreiber, A. Voelkl, G. Hartmann, and S. Endres Immunostimulatory RNA oligonucleotides trigger an antigen-specific cytotoxic T-cell and IgG2a response Blood, April 1, 2007; 109(7): 2953 - 2960. [Abstract] [Full Text] [PDF] U. S. Deshmukh, H. Bagavant, D. Sim, V. Pidiyar, and S. M. Fu A SmD Peptide Induces Better Antibody Responses to Other Proteins within the Small Nuclear Ribonucleoprotein Complex than to SmD Protein via Intermolecular Epitope Spreading J. Immunol., February 15, 2007; 178(4): 2565 - 2571. [Abstract] [Full Text] [PDF] V. M. Ronnefarth, A. I. M. Erbacher, T. Lamkemeyer, J. Madlung, A. Nordheim, H.-G. Rammensee, and P. Decker TLR2/TLR4-Independent Neutrophil Activation and Recruitment upon Endocytosis of Nucleosomes Reveals a New Pathway of Innate Immunity in Systemic Lupus Erythematosus J. Immunol., December 1, 2006; 177(11): 7740 - 7749. [Abstract] [Full Text] [PDF] K. D. Smith Lupus Nephritis: Toll the Trigger! J. Am. Soc. Nephrol., December 1, 2006; 17(12): 3273 - 3275. [Full Text] [PDF] J. A. Deane and S. Bolland Nucleic Acid-Sensing TLRs as Modifiers of Autoimmunity J. Immunol., November 15, 2006; 177(10): 6573 - 6578. [Abstract] [Full Text] [PDF]

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