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

Masahiro Moritoki; Takeshi Kadowaki; Toshiro Niki; Daisuke Nakano; Genichiro Soma; Hirohito Mori; Hideki Kobara; Tsutomu Masaki; Masakazu Kohno; Mitsuomi Hirashima

doi:10.1371/journal.pone.0060807

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

PLoS One. 2013 Apr 9;8(4):e60807. doi: 10.1371/journal.pone.0060807. Print 2013.

Authors

Masahiro Moritoki¹, Takeshi Kadowaki, Toshiro Niki, Daisuke Nakano, Genichiro Soma, Hirohito Mori, Hideki Kobara, Tsutomu Masaki, Masakazu Kohno, Mitsuomi Hirashima

Affiliation

¹ Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Antinuclear / immunology
Apoptosis / drug effects*
B-Cell Activating Factor / genetics
B-Cell Activating Factor / immunology
CD8-Positive T-Lymphocytes / drug effects
CD8-Positive T-Lymphocytes / immunology
CD8-Positive T-Lymphocytes / pathology
Galectins / pharmacology*
Gene Expression Regulation
Hematocrit
Hepatitis A Virus Cellular Receptor 2
Lupus Erythematosus, Systemic / drug therapy*
Lupus Erythematosus, Systemic / genetics
Lupus Erythematosus, Systemic / immunology
Lupus Erythematosus, Systemic / pathology
Lymphocyte Activation / drug effects*
Mice
Mice, Inbred MRL lpr
Plasma Cells / drug effects*
Plasma Cells / immunology
Plasma Cells / pathology
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
Th1 Cells / drug effects
Th1 Cells / immunology
Th1 Cells / pathology
Th17 Cells / drug effects
Th17 Cells / immunology
Th17 Cells / pathology

Substances

Antibodies, Antinuclear
B-Cell Activating Factor
Galectins
Havcr2 protein, mouse
Hepatitis A Virus Cellular Receptor 2
Receptors, Virus
Tnfsf13b protein, mouse
galectin 9, mouse

Grants and funding

This work was supported, in part, by Scientific Research (C) 2010 - (22590360) and Scientific Research (A) 2011 - (23256004) from the Japan Society for Promotion of Science. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.