title: Splenic phagocytes promote responses to nucleosomes in (NZB x NZW) F1 mice.
abstract: Autoantigen presentation to T cells is crucial for the development of autoimmune disease. However, the mechanisms of autoantigen presentation are poorly understood. In this study, we show that splenic phagocytes play an important role in autoantigen presentation in murine lupus. Nucleosomes are major autoantigens in systemic lupus erythematosus. We found that nucleosome-specific T cells were stimulated dominantly in the spleen, compared with lymph nodes, lung, and thymus. Among splenic APCs, F4/80(+) macrophages and CD11b(+)CD11c(+) dendritic cells were strong stimulators for nucleosome-specific T cells. When splenic phagocytes were depleted in (NZB x NZW) F(1) (NZB/W F(1)) mice, nucleosome presentation in the spleen was dramatically suppressed. Moreover, depletion of splenic phagocytes significantly suppressed anti-nucleosome Ab and anti-dsDNA Ab production. Proteinuria progression was delayed and survival was prolonged in phagocyte-depleted mice. The numbers of autoantibody- secreting cells were decreased in the spleen from phagocyte-depleted mice. Multiple injections of splenic F4/80(+) macrophages, not those of splenic CD11c(+) dendritic cells, induced autoantibody production and proteinuria progression in NZB/W F(1) mice. These results indicate that autoantigen presentation by splenic phagocytes including macrophages significantly contributes to autoantibody production and disease progression in lupus-prone mice.
authors.affiliation: Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Okamoto
authors.forename: Keishi
authors.initials: K
authors.lastname: Fujio
authors.forename: Nico
authors.initials: N
authors.lastname: van Rooijen
authors.forename: Nelson H
authors.initials: NH
authors.lastname: Tsuno
authors.forename: Koki
authors.initials: K
authors.lastname: Takahashi
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Tsurui
authors.forename: Sachiko
authors.initials: S
authors.lastname: Hirose
authors.forename: Keith B
authors.initials: KB
authors.lastname: Elkon
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology; D017951:Antigen Presentation / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D039481:CD11b Antigen / Q000276:immunology; D039521:CD11c Antigen / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology / Q000637:transplantation; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D051379:Mice; D009707:Nucleosomes / Q000276:immunology*; D009928:Organ Specificity / Q000276:immunology; D010950:Plasma Cells / Q000276:immunology / Q000473:pathology; D011507:Proteinuria / Q000276:immunology / Q000473:pathology; D013045:Species Specificity; D013154:Spleen / Q000276:immunology* / Q000473:pathology
chemical_list: D000974:Antibodies, Antinuclear; D001324:Autoantigens; D039481:CD11b Antigen; D039521:CD11c Antigen; D009707:Nucleosomes