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.
Copyright © 2012 Elsevier Inc. All rights reserved.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Acetylgalactosamine / analogs & derivatives
-
Acetylgalactosamine / pharmacology
-
Animals
-
Benzyl Compounds / pharmacology
-
Cells, Cultured
-
Encephalomyelitis, Autoimmune, Experimental / genetics
-
Encephalomyelitis, Autoimmune, Experimental / immunology
-
Encephalomyelitis, Autoimmune, Experimental / metabolism
-
Female
-
Flow Cytometry
-
Forkhead Transcription Factors / immunology
-
Forkhead Transcription Factors / metabolism
-
Galectins / genetics
-
Galectins / immunology*
-
Galectins / metabolism
-
Hepatitis A Virus Cellular Receptor 2
-
Interleukin-17 / immunology
-
Interleukin-17 / metabolism
-
Interleukin-2 / immunology*
-
Interleukin-2 / metabolism
-
Interleukin-2 Receptor alpha Subunit / immunology
-
Interleukin-2 Receptor alpha Subunit / metabolism
-
Interleukin-6 / pharmacology
-
Male
-
Mice
-
Mice, Inbred C57BL
-
Mice, Knockout
-
Receptors, Virus / immunology*
-
Receptors, Virus / metabolism
-
T-Lymphocytes, Regulatory / immunology
-
T-Lymphocytes, Regulatory / metabolism
-
Th17 Cells / drug effects
-
Th17 Cells / immunology*
-
Th17 Cells / metabolism
-
Transforming Growth Factor beta1 / pharmacology
Substances
-
Benzyl Compounds
-
Forkhead Transcription Factors
-
Foxp3 protein, mouse
-
Galectins
-
Havcr2 protein, mouse
-
Hepatitis A Virus Cellular Receptor 2
-
Interleukin-17
-
Interleukin-2
-
Interleukin-2 Receptor alpha Subunit
-
Interleukin-6
-
Receptors, Virus
-
Transforming Growth Factor beta1
-
galectin 9, mouse
-
benzyl-alpha-N-acetylgalactosamine
-
Acetylgalactosamine