title: Elimination of Granulocytic Myeloid-Derived Suppressor Cells in Lupus-Prone Mice Linked to Reactive Oxygen Species-Dependent Extracellular Trap Formation.
abstract: OBJECTIVE
  Emerging evidence supports a crucial role of myeloid-derived suppressor cells (MDSCs) in the regulation of autoimmune diseases. However, their role in systemic lupus erythematosus (SLE) remains unknown. This study sought to address the role of MDSCs in the pathogenesis of SLE.
  
  
  METHODS
  MDSCs from (NZB × NZW)F1 lupus-prone mice were assessed for phenotype by flow cytometry, and the function of MDSCs was analyzed by in vitro T cell proliferation assay and real-time quantitative polymerase chain reaction. Extracellular trap (ET) formation was evaluated by immunofluorescence and confocal microscopy. The production of reactive oxygen species (ROS) by Ly-6G+ cells was determined by fluorescence-activated cell sorting analysis.
  
  
  RESULTS
  Expansion of MDSCs was impaired and the function of MDSCs was defective in the lymphoid organs of (NZB × NZW)F1 lupus-prone mice with established disease, in which involvement of predominantly the granulocytic MDSC (G-MDSC) cell subset was observed. More specifically, the results showed that increased elimination of G-MDSCs, driven by the inflammatory milieu of lupus, could be attributed to ET formation, and that cytokines, such as interferon-α (IFNα), IFNγ, and interleukin-6, play a role in this process. Induction of ET release by G-MDSCs was mediated by the production of ROS, since inhibition of ROS generation significantly reduced ET release.
  
  
  CONCLUSIONS
  Collectively, the results of this study reveal that elimination of a crucial regulatory immune cell subset is a feature of the SLE microenvironment. These findings provide new insights into the pathogenetic mechanisms of the disease.
authors.affiliation: Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology, Heraklion, Greece, Laboratory of Autoimmunity and Inflammation, University of Crete Medical School, Heraklion, Greece, and Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
authors.forename: Katerina
authors.initials: K
authors.lastname: Vlachou
authors.affiliation: Maria Glymenaki, MSc, Prodromos Sidiropoulos, MD, PhD: Laboratory of Autoimmunity and Inflammation, University of Crete Medical School, Heraklion, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Mintzas
authors.affiliation: Maria Glymenaki, MSc, Prodromos Sidiropoulos, MD, PhD: Laboratory of Autoimmunity and Inflammation, University of Crete Medical School, Heraklion, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Glymenaki
authors.affiliation: Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology and Laboratory of Autoimmunity and Inflammation, University of Crete Medical School, Heraklion, Greece.
authors.forename: Marianna
authors.initials: M
authors.lastname: Ioannou
authors.affiliation: Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology and Laboratory of Autoimmunity and Inflammation, University of Crete Medical School, Heraklion, Greece.
authors.forename: Garyfalia
authors.initials: G
authors.lastname: Papadaki
authors.affiliation: Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology and Laboratory of Autoimmunity and Inflammation, University of Crete Medical School, Heraklion, Greece.
authors.forename: George K
authors.initials: GK
authors.lastname: Bertsias
authors.affiliation: Maria Glymenaki, MSc, Prodromos Sidiropoulos, MD, PhD: Laboratory of Autoimmunity and Inflammation, University of Crete Medical School, Heraklion, Greece.
authors.forename: Prodromos
authors.initials: P
authors.lastname: Sidiropoulos
authors.affiliation: Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology, Heraklion, Greece, University of Athens Medical School, Athens, Greece, and Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
authors.forename: Dimitrios T
authors.initials: DT
authors.lastname: Boumpas
authors.affiliation: Technische Universität Dresden, Dresden, Germany, and Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
authors.forename: Panayotis
authors.initials: P
authors.lastname: Verginis
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000276:immunology; D049109:Cell Proliferation; D016207:Cytokines / Q000276:immunology*; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D065206:Extracellular Traps / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D042381:Granulocyte Precursor Cells / Q000276:immunology*; D066298:In Vitro Techniques; D016898:Interferon-alpha / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB; D018613:Microscopy, Confocal; D022423:Myeloid Cells / Q000276:immunology; D017382:Reactive Oxygen Species / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000950:Antigens, Ly; D016207:Cytokines; D016898:Interferon-alpha; D015850:Interleukin-6; C480309:Ly6G antigen, mouse; D017382:Reactive Oxygen Species; D007371:Interferon-gamma