Galectin-9 suppresses the generation of Th17, promotes the induction of regulatory T cells, and regulates experimental autoimmune arthritis

被引:407
作者
Seki, Masako [1 ]
Oomizu, Souichi [1 ]
Sakata, Ken-mei [2 ]
Sakata, Atsuko [2 ]
Arikawa, Tomohiro [1 ]
Watanabe, Kota [3 ]
Ito, Kanako [3 ]
Takeshita, Keisuke [3 ]
Niki, Toshiro [3 ]
Saita, Naoki [2 ]
Nishi, Nozomu [4 ]
Yamauchi, Akira [5 ]
Katoh, Shigeki [5 ]
Matsukawa, Akihiro [6 ]
Kuchroo, Vijay [7 ]
Hirashima, Mitsuomi [1 ]
机构
[1] Kagawa Univ, Fac Med, Dept Immunol & Immunopathol, Miki, Kagawa 7610793, Japan
[2] Kumamoto Univ, Fac Med, Dept Internal Med, Kumamoto, Japan
[3] Galpharma Co Ltd, Kagawa, Japan
[4] Kagawa Univ, Fac Med, Dept Endocrinol, Kagawa, Japan
[5] Kagawa Univ, Fac Med, Dept Cell Regulat, Kagawa, Japan
[6] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Pathol & Expt Med, Okayama 7008530, Japan
[7] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA
关键词
rodent; collagen-induced arthritis; galectin-9; th1; th17; regulatory T cells; pro-inflammatory cytokines; T cell immunoglobulin and mucin domain-containing molecule 3;
D O I
10.1016/j.clim.2008.01.006
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The effects of galectin-9 on a mouse collagen-induced arthritis (CIA) model were assessed to clarify whether galectin-9 suppresses CIA by regulating T cell. immune responses. Galectin-9 suppressed CIA in a dose-dependent manner, and such suppression was observed even when treatment was started on 7 days after the booster, indicating its preventive and therapeutic effects. Galectin-9 induced the decreased levels of pro-inflammatory cytokines, IL-17, IL-12, and IFN gamma in the joint. Gatectin-9 induced the decreased number of CD4(+) TIM-3(+) T cells in peripheral blood. Galectin-9-deficient mice became susceptible to CIA may be by increased number of CD4(+) TIM-3(+) T cells and decreased number of Treg cells. We further found that galectin-9 induces differentiation of naive T cells to Treg cells, and it suppresses differentiation to Th17 cells in vitro. The present results suggested that galectin-9 ameliorates CIA by suppressing the generation of Th17, promoting the induction of regulatory T cells. (C) 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码:78 / 88
页数:11
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