title: Siglec-1-positive plasmacytoid dendritic cells (pDCs) in human peripheral blood: A semi-mature and myeloid-like subset imbalanced during protective and autoimmune responses.
abstract: Plasmacytoid dendritic cells (pDCs) play a central role in the pathogenesis of systemic lupus erythematosus (SLE) as IFN-α producers and promoters of T-cell activation or tolerance. Here, we demonstrated by flow-cytometry and confocal microscopy that Siglec-1, a molecule involved in the regulation of adaptive immunoresponses, is expressed in a subset of semi-mature, myeloid-like pDCs in human blood. These pDCs express lower BDCA-2 and CD123 and higher HLA-DR and CD11c than Siglec-1-negative pDCs and do not produce IFN-α via TLR7/TLR9 engagement. In vitro, Siglec-1 expression was induced in Siglec-1-negative pDCs by influenza virus. Proportions of Siglec-1-positive/Siglec-1-negative pDCs were higher in SLE than in healthy controls and correlated with disease activity. Healthy donors immunized with yellow fever vaccine YFV-17D displayed different kinetics of the two pDC subsets during protective immune response. PDCs can be subdivided into two subsets according to Siglec-1 expression. These subsets may play specific roles in (auto)immune responses.
authors.affiliation: Ruprecht-Karls-University, Grabengasse 1, 69117 Heidelberg, Germany.
authors.forename: Theresa R
authors.initials: TR
authors.lastname: Wilhelm
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité University Hospital, Charitéplatz 1, 10117, Berlin, Germany; German Rheumatism Research Centre (DRFZ) - a Leibniz Institute, Charitéplatz 1, 10117, Berlin, Germany.
authors.forename: Adriano
authors.initials: A
authors.lastname: Taddeo
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité University Hospital, Charitéplatz 1, 10117, Berlin, Germany; German Rheumatism Research Centre (DRFZ) - a Leibniz Institute, Charitéplatz 1, 10117, Berlin, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Winter
authors.affiliation: Regenerative Immunology and Aging, Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité University Medicine CVK, Augustenburger Platz 1, 13353, Berlin, Germany; German Rheumatism Research Centre (DRFZ) - a Leibniz Institute, Charitéplatz 1, 10117, Berlin, Germany.
authors.forename: Axel Ronald
authors.initials: AR
authors.lastname: Schulz
authors.affiliation: Regenerative Immunology and Aging, Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité University Medicine CVK, Augustenburger Platz 1, 13353, Berlin, Germany.
authors.forename: Julia-Nora
authors.initials: JN
authors.lastname: Mälzer
authors.affiliation: Center for Biological Threats and Special Pathogens 1, Robert Koch-Institute, Nordufer 20, 13353, Berlin, Germany.
authors.forename: Cristina
authors.initials: C
authors.lastname: Domingo
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité University Hospital, Charitéplatz 1, 10117, Berlin, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Biesen
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité University Hospital, Charitéplatz 1, 10117, Berlin, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Alexander
authors.affiliation: Regenerative Immunology and Aging, Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité University Medicine CVK, Augustenburger Platz 1, 13353, Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Thiel
authors.affiliation: German Rheumatism Research Centre (DRFZ) - a Leibniz Institute, Charitéplatz 1, 10117, Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Radbruch
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité University Hospital, Charitéplatz 1, 10117, Berlin, Germany; German Rheumatism Research Centre (DRFZ) - a Leibniz Institute, Charitéplatz 1, 10117, Berlin, Germany.
authors.forename: Falk
authors.initials: F
authors.lastname: Hiepe
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité University Hospital, Charitéplatz 1, 10117, Berlin, Germany; German Rheumatism Research Centre (DRFZ) - a Leibniz Institute, Charitéplatz 1, 10117, Berlin, Germany. Electronic address: gerl@drfz.de.
authors.forename: Velia
authors.initials: V
authors.lastname: Gerl
mesh_terms: D000328:Adult; D001327:Autoimmune Diseases / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology; D016022:Case-Control Studies; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D066298:In Vitro Techniques; D007252:Influenza Vaccines / Q000494:pharmacology*; D016898:Interferon-alpha / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D022423:Myeloid Cells / Q000276:immunology; D063267:Sialic Acid Binding Ig-like Lectin 1 / Q000378:metabolism*; D051217:Toll-Like Receptor 9 / Q000276:immunology; D022341:Yellow Fever Vaccine / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D007252:Influenza Vaccines; D016898:Interferon-alpha; C571166:SIGLEC1 protein, human; D063267:Sialic Acid Binding Ig-like Lectin 1; D051217:Toll-Like Receptor 9; D022341:Yellow Fever Vaccine
keywords: Erythematosus; Plasmacytoide dendritic cell; Siglec-1; Systemic lupus