title: Clusterin facilitates apoptotic cell clearance and prevents apoptotic cell-induced autoimmune responses.
abstract: Clusterin (Clu), an extracellular chaperone, exhibits characteristics of soluble innate immunity receptors, as assessed by its ability to bind some bacteria strains. In this study, we report that Clu also binds specifically to late apoptotic cells but not to live, early apoptotic, or necrotic cells. Histones, which accumulate on blebs during the apoptotic process, represent privileged Clu-binding motifs at the surface of late apoptotic cells. As a consequence, Clu potentiates, both in vitro and in vivo, the phagocytosis of late apoptotic cells by macrophages. Moreover, the increased phagocytosis of late apoptotic cells induced by Clu favors the presentation and cross-presentation of apoptotic cell-associated antigens. Finally, we observed that, in a model of apoptotic cell-induced autoimmunity, and relative to control mice, Clu(-/-) mice develop symptoms of autoimmunity, including the generation of anti-dsDNA antibodies, deposition of immunoglobulins and complement components within kidneys, and splenomegaly. These results identify Clu as a new molecule partner involved in apoptotic cell efferocytosis and suggest a protective role for Clu in inflammation and autoimmune diseases.
authors.affiliation: Université d'Angers, Angers, France.|Unit 892, Inserm, CHU d'Angers, Angers, France.|CNRS, Unit 6299, Angers, France.|LabEx IGO "Immuno-Graft-Onco", Angers, France.
authors.forename: P
authors.initials: P
authors.lastname: Cunin
authors.affiliation: Université d'Angers, Angers, France.|Unit 892, Inserm, CHU d'Angers, Angers, France.|CNRS, Unit 6299, Angers, France.|LabEx IGO "Immuno-Graft-Onco", Angers, France.|Laboratoire d'Immunologie et d'Allergologie, CHU Angers, Angers, France.
authors.forename: C
authors.initials: C
authors.lastname: Beauvillain
authors.affiliation: Université d'Angers, Angers, France.|Unit 892, Inserm, CHU d'Angers, Angers, France.|CNRS, Unit 6299, Angers, France.|LabEx IGO "Immuno-Graft-Onco", Angers, France.
authors.forename: C
authors.initials: C
authors.lastname: Miot
authors.affiliation: Université d'Angers, Angers, France.|Unit 892, Inserm, CHU d'Angers, Angers, France.|CNRS, Unit 6299, Angers, France.|LabEx IGO "Immuno-Graft-Onco", Angers, France.|Service de Néphrologie-Dialyse-Transplantation, CHU Angers, Angers, France.
authors.forename: J-F
authors.initials: JF
authors.lastname: Augusto
authors.affiliation: Université d'Angers, Angers, France.|Unit 892, Inserm, CHU d'Angers, Angers, France.|CNRS, Unit 6299, Angers, France.|LabEx IGO "Immuno-Graft-Onco", Angers, France.
authors.forename: L
authors.initials: L
authors.lastname: Preisser
authors.affiliation: Université d'Angers, Angers, France.|Unit 892, Inserm, CHU d'Angers, Angers, France.|CNRS, Unit 6299, Angers, France.|LabEx IGO "Immuno-Graft-Onco", Angers, France.|Laboratoire d'Immunologie et d'Allergologie, CHU Angers, Angers, France.
authors.forename: S
authors.initials: S
authors.lastname: Blanchard
authors.affiliation: Université d'Angers, Angers, France.|Unit 892, Inserm, CHU d'Angers, Angers, France.|CNRS, Unit 6299, Angers, France.|LabEx IGO "Immuno-Graft-Onco", Angers, France.
authors.forename: P
authors.initials: P
authors.lastname: Pignon
authors.affiliation: Université d'Angers, Angers, France.|Unit 892, Inserm, CHU d'Angers, Angers, France.|CNRS, Unit 6299, Angers, France.|LabEx IGO "Immuno-Graft-Onco", Angers, France.
authors.forename: M
authors.initials: M
authors.lastname: Scotet
authors.affiliation: Université d'Angers, Angers, France.|Unit 892, Inserm, CHU d'Angers, Angers, France.|CNRS, Unit 6299, Angers, France.|LabEx IGO "Immuno-Graft-Onco", Angers, France.
authors.forename: E
authors.initials: E
authors.lastname: Garo
authors.affiliation: Université d'Angers, Angers, France.|Unit 892, Inserm, CHU d'Angers, Angers, France.|CNRS, Unit 6299, Angers, France.|LabEx IGO "Immuno-Graft-Onco", Angers, France.
authors.forename: I
authors.initials: I
authors.lastname: Fremaux
authors.affiliation: Université d'Angers, Angers, France.|Unit 892, Inserm, CHU d'Angers, Angers, France.|CNRS, Unit 6299, Angers, France.|LabEx IGO "Immuno-Graft-Onco", Angers, France.|Laboratoire d'Immunologie et d'Allergologie, CHU Angers, Angers, France.
authors.forename: A
authors.initials: A
authors.lastname: Chevailler
authors.affiliation: Université d'Angers, Angers, France.|Unit 892, Inserm, CHU d'Angers, Angers, France.|CNRS, Unit 6299, Angers, France.|LabEx IGO "Immuno-Graft-Onco", Angers, France.|Service de Néphrologie-Dialyse-Transplantation, CHU Angers, Angers, France.
authors.forename: J-F
authors.initials: JF
authors.lastname: Subra
authors.affiliation: Université Victor Segalen, Bordeaux, France.|CNRS Unit 5164, Bordeaux, France.|CHU Bordeaux, Bordeaux, France.
authors.forename: P
authors.initials: P
authors.lastname: Blanco
authors.affiliation: School of Biological Sciences, Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, New South Wales, Australia.
authors.forename: M R
authors.initials: MR
authors.lastname: Wilson
authors.affiliation: Université d'Angers, Angers, France.|Unit 892, Inserm, CHU d'Angers, Angers, France.|CNRS, Unit 6299, Angers, France.|LabEx IGO "Immuno-Graft-Onco", Angers, France.|Laboratoire d'Immunologie et d'Allergologie, CHU Angers, Angers, France.
authors.forename: P
authors.initials: P
authors.lastname: Jeannin
authors.affiliation: Université d'Angers, Angers, France.|Unit 892, Inserm, CHU d'Angers, Angers, France.|CNRS, Unit 6299, Angers, France.|LabEx IGO "Immuno-Graft-Onco", Angers, France.|Laboratoire d'Immunologie et d'Allergologie, CHU Angers, Angers, France.
authors.forename: Y
authors.initials: Y
authors.lastname: Delneste
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D017951:Antigen Presentation / Q000235:genetics*; D017209:Apoptosis / Q000276:immunology; D001324:Autoantigens / Q000235:genetics / Q000276:immunology*; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D051152:Clusterin / Q000235:genetics / Q000276:immunology*; D018920:Coculture Techniques; D045142:Cross-Priming / Q000235:genetics; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D015870:Gene Expression; D006801:Humans; D007668:Kidney / Q000276:immunology / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010587:Phagocytosis; D061251:Primary Cell Culture; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013163:Splenomegaly / Q000235:genetics / Q000276:immunology* / Q000473:pathology
chemical_list: D000974:Antibodies, Antinuclear; D001324:Autoantigens; C495242:CLU protein, human; C495243:Clu protein, mouse; D051152:Clusterin