title: IL-10 mediates plasmacytosis-associated immunodeficiency by inhibiting complement-mediated neutrophil migration.
abstract: Plasmacytosis (ie, an expansion of plasma cell populations to much greater than the homeostatic level) occurs in the context of various immune disorders and plasma cell neoplasia. This condition is often associated with immunodeficiency that causes increased susceptibility to severe infections. Yet a causative link between plasmacytosis and immunodeficiency has not been established.
  
  
  
  Because recent studies have identified plasma cells as a relevant source of the immunosuppressive cytokine IL-10, we sought to investigate the role of IL-10 during conditions of polyclonal and neoplastic plasmacytosis for the regulation of immunity and its effect on inflammation and immunodeficiency.
  
  
  
  We used flow cytometry, IL-10 reporter (Vert-X) and B cell-specific IL-10 knockout mice, migration assays, and antibody-mediated IL-10 receptor blockade to study plasmacytosis-associated IL-10 expression and its effect on inflammation and Streptococcus pneumoniae infection in mice. ELISA was used to quantify IL-10 levels in patients with myeloma.
  
  
  
  IL-10 production was a common feature of normal and neoplastic plasma cells in mice, and IL-10 levels increased with myeloma progression in patients. IL-10 directly inhibited neutrophil migration toward the anaphylatoxin C5a and suppressed neutrophil-dependent inflammation in a murine model of autoimmune disease. MOPC.315.BM murine myeloma leads to an increased incidence of bacterial infection in the airways, which was reversed after IL-10 receptor blockade.
  
  
  
  We provide evidence that plasmacytosis-associated overexpression of IL-10 inhibits neutrophil migration and neutrophil-mediated inflammation but also promotes immunodeficiency.
authors.affiliation: Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany; Institute of Immunology, University Hospital Jena, Jena, Germany.
authors.forename: Upasana
authors.initials: U
authors.lastname: Kulkarni
authors.affiliation: Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany.
authors.forename: Christian M
authors.initials: CM
authors.lastname: Karsten
authors.affiliation: Department Genetics of Microorganisms, Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kohler
authors.affiliation: Department Genetics of Microorganisms, Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Hammerschmidt
authors.affiliation: Comprehensive Cancer Centre Mainfranken, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Kurt
authors.initials: K
authors.lastname: Bommert
authors.affiliation: Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Tiburzy
authors.affiliation: Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany.
authors.forename: Lingzhang
authors.initials: L
authors.lastname: Meng
authors.affiliation: Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany.
authors.forename: Lara
authors.initials: L
authors.lastname: Thieme
authors.affiliation: Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Recke
authors.affiliation: Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany.
authors.forename: Ralf J
authors.initials: RJ
authors.lastname: Ludwig
authors.affiliation: Charité-University Medicine Berlin, Department of Rheumatology, and German Arthritis Research Center, Berlin, Germany.
authors.forename: Karolin
authors.initials: K
authors.lastname: Pollok
authors.affiliation: Institute of Anatomy, University of Lübeck, Lübeck, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Kalies
authors.affiliation: Centre for Immune Regulation and KG Jebsen Centre for Influenza Vaccine Research, Institute of Immunology, University of Oslo and Oslo University Hospital, Oslo, Norway.
authors.forename: Bjarne
authors.initials: B
authors.lastname: Bogen
authors.affiliation: Institute of Immunology, University Hospital Jena, Jena, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Boettcher
authors.affiliation: Institute of Immunology, University Hospital Jena, Jena, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kamradt
authors.affiliation: Charité-University Medicine Berlin, Department of Rheumatology, and German Arthritis Research Center, Berlin, Germany.
authors.forename: Anja E
authors.initials: AE
authors.lastname: Hauser
authors.affiliation: Department of Internal Medicine III, University of Ulm, Ulm, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Langer
authors.affiliation: Department of Orthopaedic Trauma, Hand, Plastic and Reconstruction Surgery, University of Ulm, Ulm, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Huber-Lang
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, University of Cincinnati College of Medicine, and the Department of Medicine, Cincinnati Veterans Affairs Medical Center, Cincinnati, Ohio; Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Fred D
authors.initials: FD
authors.lastname: Finkelman
authors.affiliation: Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany; Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Jörg
authors.initials: J
authors.lastname: Köhl
authors.affiliation: Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany.
authors.forename: David M
authors.initials: DM
authors.lastname: Wong
authors.affiliation: Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany. Electronic address: Rudolf.Manz@uksh.de.
authors.forename: Rudolf Armin
authors.initials: RA
authors.lastname: Manz
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015936:Complement C5a / Q000276:immunology; D006801:Humans; D007154:Immune System Diseases / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology*; D007960:Leukocyte Disorders / Q000276:immunology; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009101:Multiple Myeloma / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D010950:Plasma Cells / Q000276:immunology*; D011008:Pneumococcal Infections / Q000276:immunology
chemical_list: D016753:Interleukin-10; D015936:Complement C5a
keywords: IL-10; Plasmacytosis; immunodeficiency; inflammation; neutrophil