Galectin-9 ameliorates clinical severity of MRL/lpr lupus-prone mice by inducing plasma cell apoptosis independently of Tim-3

• Published in: PloS one 2013-04, Vol.8 (4), p.e60807-e60807
• Main Authors: Moritoki, Masahiro, Kadowaki, Takeshi, Niki, Toshiro, Nakano, Daisuke, Soma, Genichiro, Mori, Hirohito, Kobara, Hideki, Masaki, Tsutomu, Kohno, Masakazu, Hirashima, Mitsuomi
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Anti-DNA antibodies; Antibodies; Antibodies, Antinuclear - immunology; Apoptosis; Apoptosis - drug effects; Arthritis; Autoimmune diseases; B cells; B-Cell Activating Factor - genetics; B-Cell Activating Factor - immunology; Biology; Blocking; Blocking antibodies; BLyS protein; Bone marrow; CD19 antigen; CD8 antigen; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - pathology; Galectin-9; Galectins - pharmacology; Gastroenterology; Gene Expression Regulation; Helper cells; Hematocrit; Hepatitis A Virus Cellular Receptor 2; Immunology; Inflammation; Laboratory animals; Lupus; Lupus Erythematosus, Systemic - drug therapy; Lupus Erythematosus, Systemic - genetics; Lupus Erythematosus, Systemic - immunology; Lupus Erythematosus, Systemic - pathology; Lymphocyte Activation - drug effects; Lymphocytes; Lymphocytes B; Lymphocytes T; Macrophages; Medical prognosis; Medicine; Mice; Mice, Inbred MRL lpr; Neurology; Pathogenesis; Plasma; Plasma cells; Plasma Cells - drug effects; Plasma Cells - immunology; Plasma Cells - pathology; Proteinuria; Proteinuria - genetics; Proteinuria - immunology; Proteinuria - pathology; Proteinuria - prevention & control; Receptors, Virus - antagonists & inhibitors; Receptors, Virus - genetics; Receptors, Virus - immunology; Severity of Illness Index; Signal Transduction; Systemic lupus erythematosus; T cells; Th1 Cells - drug effects; Th1 Cells - immunology; Th1 Cells - pathology; Th17 Cells - drug effects; Th17 Cells - immunology; Th17 Cells - pathology
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0060807

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.