title: IgE Inhibits Toll-like Receptor 7- and Toll-like Receptor 9-Mediated Expression of Interferon-α by Plasmacytoid Dendritic Cells in Patients With Systemic Lupus Erythematosus.
abstract: Plasmacytoid dendritic cells (PDCs) play a central role in pathogenesis of systemic lupus erythematosus (SLE) through their unique ability to produce large amounts of type I interferon (IFN) upon Toll-like receptor 7 (TLR-7) and TLR-9 triggering. PDCs express specific surface regulatory receptors involved in negative regulation of IFNα secretion. These receptors use the γ-chain of high-affinity Fc receptor (FcR) for IgE, FcɛRI. We undertook this study to test our hypothesis that IgE engagement of FcɛRI on PDCs may impact IFNα production in SLE patients.
  
  
  
  Serum levels of total IgE were measured in healthy volunteers, SLE patients, and patients with IgE-dependent allergic disorders. FcɛRI expression on PDCs from SLE patients was evaluated by flow cytometry. Purified PDCs were incubated with monoclonal IgE for 24 hours, then stimulated for 18 hours with TLR agonists or immune complexes (ICs). IFNα production by PDCs was detected by quantitative real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay. Expression of TLR-7, TLR-9, and IFN regulatory factor 7 (IRF-7) in PDCs was quantified by quantitative real-time PCR.
  
  
  
  We observed significantly higher IgE levels in SLE patients with quiescent disease than in those with active disease. In SLE patients, IgE levels correlated inversely with disease activity. IgE levels were not associated with the presence of antinuclear IgE. Purified PDCs treated for 24 hours with monoclonal IgE up-regulated FcɛRI expression in an IgE dose-dependent manner. IgE-treated PDCs significantly decreased IFNα secretion and down-regulated CCR7 expression upon stimulation with TLR-7 and TLR-9 ligands and ICs from lupus patients. IgE treatment down-regulated expression of TLR-9 and IRF-7.
  
  
  
  Our results support the notion that IgE plays a protective role in SLE pathogenesis through the modulation of inflammatory response by PDCs.
authors.affiliation: Université de Bordeaux and Immuno ConcEpT, CNRS-UMR 5164, Bordeaux, France.
authors.forename: Liliane
authors.initials: L
authors.lastname: Khoryati
authors.affiliation: Immuno ConcEpT, CNRS-UMR 5164, Bordeaux, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Augusto
authors.affiliation: Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Shipley
authors.affiliation: Université de Bordeaux, Immuno ConcEpT, CNRS-UMR 5164, and Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Contin-Bordes
authors.affiliation: Immuno ConcEpT, CNRS-UMR 5164, Bordeaux, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Douchet
authors.affiliation: Immuno ConcEpT, CNRS-UMR 5164, and Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Mitrovic
authors.affiliation: Université de Bordeaux, Immuno ConcEpT, CNRS-UMR 5164, and Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.
authors.forename: Marie-Elise
authors.initials: ME
authors.lastname: Truchetet
authors.affiliation: Université de Bordeaux, Immuno ConcEpT, CNRS-UMR 5164, and Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.
authors.forename: Estibaliz
authors.initials: E
authors.lastname: Lazaro
authors.affiliation: Université de Bordeaux, Immuno ConcEpT, CNRS-UMR 5164, and Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Duffau
authors.affiliation: Université de Bordeaux, Immuno ConcEpT, CNRS-UMR 5164, and Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Couzi
authors.affiliation: Université de Bordeaux and Immuno ConcEpT, CNRS-UMR 5164, Bordeaux, France.
authors.forename: Clément
authors.initials: C
authors.lastname: Jacquemin
authors.affiliation: Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Barnetche
authors.affiliation: Université de Bordeaux and INSERM U916, Institut Bergonié, Bordeaux, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Vacher
authors.affiliation: Université de Bordeaux and Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Schaeverbeke
authors.affiliation: Université de Bordeaux, Immuno ConcEpT, CNRS-UMR 5164, and Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Blanco
authors.affiliation: Université de Bordeaux, Immuno ConcEpT, CNRS-UMR 5164, and Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Richez
mesh_terms: D002478:Cells, Cultured; D003713:Dendritic Cells / Q000502:physiology*; D006801:Humans; D007073:Immunoglobulin E / Q000502:physiology*; D016898:Interferon-alpha / Q000096:biosynthesis*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D051199:Toll-Like Receptor 7 / Q000276:immunology*; D051217:Toll-Like Receptor 9 / Q000276:immunology*
chemical_list: D016898:Interferon-alpha; C495348:TLR7 protein, human; C495371:TLR9 protein, human; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9; D007073:Immunoglobulin E