title: Galectin-9 ameliorates clinical severity of MRL/lpr lupus-prone mice by inducing plasma cell apoptosis independently of Tim-3.
abstract: Galectin-9 ameliorates various murine autoimmune disease models by regulating T cells and macrophages, although it is not known what role it may have in B cells. The present experiment shows that galectin-9 ameliorates a variety of clinical symptoms, such as proteinuria, arthritis, and hematocrit in MRL/lpr lupus-prone mice. As previously reported, galectin-9 reduces the frequency of Th1, Th17, and activated CD8(+) T cells. Although anti-dsDNA antibody was increased in MRL/lpr lupus-prone mice, galectin-9 suppressed anti-dsDNA antibody production, at least partly, by decreasing the number of plasma cells. Galectin-9 seemed to decrease the number of plasma cells by inducing plasma cell apoptosis, and not by suppressing BAFF production. Although about 20% of CD19(-/low) CD138(+) plasma cells expressed Tim-3 in MRL/lpr lupus-prone mice, Tim-3 may not be directly involved in the galectin-9-induced apoptosis, because anti-Tim-3 blocking antibody did not block galectin-9-induced apoptosis. This is the first report of plasma cell apoptosis being induced by galectin-9. Collectively, it is likely that galectin-9 attenuates the clinical severity of MRL lupus-prone mice by regulating T cell function and inducing plasma cell apoptosis.
authors.affiliation: Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Moritoki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kadowaki
authors.forename: Toshiro
authors.initials: T
authors.lastname: Niki
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nakano
authors.forename: Genichiro
authors.initials: G
authors.lastname: Soma
authors.forename: Hirohito
authors.initials: H
authors.lastname: Mori
authors.forename: Hideki
authors.initials: H
authors.lastname: Kobara
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Masaki
authors.forename: Masakazu
authors.initials: M
authors.lastname: Kohno
authors.forename: Mitsuomi
authors.initials: M
authors.lastname: Hirashima
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects*; D053264:B-Cell Activating Factor / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D037161:Galectins / Q000494:pharmacology*; D005786:Gene Expression Regulation; D006400:Hematocrit; D000072597:Hepatitis A Virus Cellular Receptor 2; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D019463:Mice, Inbred MRL lpr; D010950:Plasma Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D011507:Proteinuria / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D011991:Receptors, Virus / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D012720:Severity of Illness Index; D015398:Signal Transduction; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology
chemical_list: D000974:Antibodies, Antinuclear; D053264:B-Cell Activating Factor; D037161:Galectins; C442241:Havcr2 protein, mouse; D000072597:Hepatitis A Virus Cellular Receptor 2; D011991:Receptors, Virus; C505720:Tnfsf13b protein, mouse; C508186:galectin 9, mouse