title: Early, transient depletion of plasmacytoid dendritic cells ameliorates autoimmunity in a lupus model.
abstract: Plasmacytoid dendritic cells (pDCs) have long been implicated in the pathogenesis of lupus. However, this conclusion has been largely based on a correlative link between the copious production of IFN-α/β by pDCs and the IFN-α/β "signature" often seen in human lupus patients. The specific contribution of pDCs to disease in vivo has not been investigated in detail. For this reason, we generated a strain of BXSB lupus-prone mice in which pDCs can be selectively depleted in vivo. Early, transient ablation of pDCs before disease initiation resulted in reduced splenomegaly and lymphadenopathy, impaired expansion and activation of T and B cells, reduced antibodies against nuclear autoantigens and improved kidney pathology. Amelioration of pathology coincided with decreased transcription of IFN-α/β-induced genes in tissues. PDC depletion had an immediate impact on the activation of immune cells, and importantly, the beneficial effects on pathology were sustained even though pDCs later recovered, indicating an early pDC contribution to disease. Together, our findings demonstrate a critical function for pDCs during the IFN-α/β-dependent initiation of autoimmune lupus and point to pDCs as an attractive therapeutic target for the treatment of SLE.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Rowland
authors.affiliation: Respiratory, Inflammation and Autoimmunity Research Department, MedImmune, Gaithersburg, MD 20878.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Riggs
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Susan
authors.initials: S
authors.lastname: Gilfillan
authors.affiliation: Department of Pathology, University of Brescia, 25123 Brescia, Italy.
authors.forename: Mattia
authors.initials: M
authors.lastname: Bugatti
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110 Department of Pathology, University of Brescia, 25123 Brescia, Italy.
authors.forename: William
authors.initials: W
authors.lastname: Vermi
authors.affiliation: Respiratory, Inflammation and Autoimmunity Research Department, MedImmune, Gaithersburg, MD 20878.
authors.forename: Roland
authors.initials: R
authors.lastname: Kolbeck
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Emil R
authors.initials: ER
authors.lastname: Unanue
authors.affiliation: Respiratory, Inflammation and Autoimmunity Research Department, MedImmune, Gaithersburg, MD 20878.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Sanjuan
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110 mcolonna@pathology.wustl.edu.
authors.forename: Marco
authors.initials: M
authors.lastname: Colonna
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005921:Glomerulonephritis / Q000209:etiology / Q000473:pathology*; D016898:Interferon-alpha / Q000378:metabolism; D016899:Interferon-beta / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D060888:Real-Time Polymerase Chain Reaction; D018709:Statistics, Nonparametric
chemical_list: D016898:Interferon-alpha; D016899:Interferon-beta