title: IFN-γ licenses CD11b(+) cells to induce progression of systemic lupus erythematosus.
abstract: Autoantibodies are a hallmark of autoimmune diseases, such as rheumatoid arthritis, autoimmune hepatitis, and systemic lupus erythematosus (SLE). High titers of anti-nuclear antibodies are used as surrogate marker for SLE, however their contribution to pathogenesis remains unclear. Using murine model of SLE and human samples, we studied the effect of immune stimulation on relapsing of SLE. Although autoantibodies bound to target cells in vivo, only additional activation of CD8(+) T cells converted this silent autoimmunity into overt disease. In mice as well as in humans CD8(+) T cells derived IFN-γ enhanced expression of Fc-receptors on CD11b(+) cells. High expression of Fc-receptors allowed CD11b(+) cells to bind to antibody covered target cells and to destroy them in vivo. We found that autoantibodies induce clinically relevant disease when adaptive immunity, specific for disease non-related antigen, is activated.
authors.affiliation: Institute of Immunology, Medical Faculty, University Duisburg-Essen, Essen, Germany; Department of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
authors.forename: Namir
authors.initials: N
authors.lastname: Shaabani
authors.affiliation: Institute of Immunology, Medical Faculty, University Duisburg-Essen, Essen, Germany; Department of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Honke
authors.affiliation: Department for Nephrology, Medical Faculty, University Duisburg-Essen, Essen, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Dolff
authors.affiliation: Department of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
authors.forename: Boris
authors.initials: B
authors.lastname: Görg
authors.affiliation: Institute of Immunology, Medical Faculty, University Duisburg-Essen, Essen, Germany.
authors.forename: Vishal
authors.initials: V
authors.lastname: Khairnar
authors.affiliation: Institute of Immunology, Medical Faculty, University Duisburg-Essen, Essen, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Merches
authors.affiliation: Institute of Immunology, Medical Faculty, University Duisburg-Essen, Essen, Germany.
authors.forename: Vikas
authors.initials: V
authors.lastname: Duhan
authors.affiliation: Metabolomics Facility, Cologne Biocenter, University Cologne, Cologne, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Metzger
authors.affiliation: Clinic for Primary Immunodeficiency, Medical Outpatient Unit and Immunodeficiency Lab, Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
authors.forename: Mike
authors.initials: M
authors.lastname: Recher
authors.affiliation: Department of Laboratory Medicine, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
authors.forename: Carmen
authors.initials: C
authors.lastname: Barthuber
authors.affiliation: Institute of Immunology, Medical Faculty, University Duisburg-Essen, Essen, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Hardt
authors.affiliation: Institute of Pharmaceutical Biology and Biotechnology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Proksch
authors.affiliation: Department of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Häussinger
authors.affiliation: Department for Nephrology, Medical Faculty, University Duisburg-Essen, Essen, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Witzke
authors.affiliation: Department of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany; Department of Molecular Medicine II, Heinrich-Heine-University Düssledorf, Düsseldorf, Germany.
authors.forename: Philipp A
authors.initials: PA
authors.lastname: Lang
authors.affiliation: Institute of Immunology, Medical Faculty, University Duisburg-Essen, Essen, Germany; Department of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany. Electronic address: karlsebastian.lang@uk-essen.de.
authors.forename: Karl S
authors.initials: KS
authors.lastname: Lang
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology; D039481:CD11b Antigen / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D017452:Receptors, IgG / Q000235:genetics; D012008:Recurrence
chemical_list: D001323:Autoantibodies; D039481:CD11b Antigen; D017452:Receptors, IgG; D007371:Interferon-gamma
keywords: Autoantibodies; Fcgr2b; IFN-γ; Infection; Inflammation; Systemic lupus erythematosus; Virus