Galectin-9 suppresses Th17 cell development in an IL-2-dependent but Tim-3-independent manner

被引:115
|
作者
Oomizu, Souichi [1 ]
Arikawa, Tomohiro [1 ]
Niki, Toshiro [1 ]
Kadowaki, Takeshi [1 ]
Ueno, Masaki [2 ]
Nishi, Nozomu [3 ]
Yamauchi, Akira [4 ]
Hirashima, Mitsuomi [1 ]
机构
[1] Kagawa Univ, Fac Med, Dept Immunol & Immunopathol, Kagawa 7610793, Japan
[2] Kagawa Univ, Fac Med, Dept Inflammat Pathol, Kagawa 7610793, Japan
[3] Kagawa Univ, Life Sci Res Ctr, Kagawa 7610793, Japan
[4] Kagawa Univ, Fac Med, Dept Cell Regulat, Kagawa 7610793, Japan
关键词
Galectin-9; Tim-3; Regulation; Th17; Treg; Differentiation; REGULATORY T-CELLS; TISSUE INFLAMMATION; DENDRITIC CELLS; IMMUNITY; TIM-3; MACROPHAGES; GENERATION; PATHWAY; BINDING; HELPER;
D O I
10.1016/j.clim.2012.01.004
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Galectin-9 (Gal-9) ameliorates autoimmune reactions by suppressing Th17 cells while augmenting Foxp3(+) regulatory T cells (Tregs). However, the exact mechanism of Gal-9-mediated immune modulation has been elusive. In a MOG-induced experimental allergic encephalomyelitis model using Gal-9(-/-) mice, we observed exacerbated inflammation and an increase in IL-17-producing Th17 cells balanced by a decrease in Foxp3+ Tregs. During in vitro Th17 skewing using TGF-beta 1 and IL-6, exogenous Gal-9 suppressed Th17 cell development and expanded Foxp3(+) Tregs from naive CD4 T cells in an IL-2-dependent manner. Although Gal-9 induced cell death in Tim3-expressing differentiated Th17 cells, Gal-9 suppressed Th17 development in a Tim-3-independent. Benzyl-alpha-GalNAc (an O-glycan biosynthesis inhibitor), but not swainsonine (a complex-type N-glycan biosynthesis inhibitor) abrogated Gal-9-mediated inhibition of Th17 development indicating that there is a linkage between Gal-9 and an unidentified glycoprotein(s) with O-linked beta-galactosides that suppress Th17 development. (C) 2012 Elsevier Inc. All rights reserved.
引用
收藏
页码:51 / 58
页数:8
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