Galectin-9 suppresses Th17 cell development in an IL-2-dependent but Tim-3-independent manner |
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Authors: | Oomizu Souichi Arikawa Tomohiro Niki Toshiro Kadowaki Takeshi Ueno Masaki Nishi Nozomu Yamauchi Akira Hirashima Mitsuomi |
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Institution: | Department of Immunology and Immunopathology, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan. |
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Abstract: | 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-β1 and IL-6, exogenous Gal-9 suppressed Th17 cell development and expanded Foxp3+ Tregs from naïve 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-α-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 β-galactosides that suppress Th17 development. |
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Keywords: | Galectin-9 Tim-3 Regulation Th17 Treg Differentiation |
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