title: Galectin-9 suppresses Th17 cell development in an IL-2-dependent but Tim-3-independent manner.
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.
authors.affiliation: Department of Immunology and Immunopathology, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan.
authors.forename: Souichi
authors.initials: S
authors.lastname: Oomizu
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Arikawa
authors.forename: Toshiro
authors.initials: T
authors.lastname: Niki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kadowaki
authors.forename: Masaki
authors.initials: M
authors.lastname: Ueno
authors.forename: Nozomu
authors.initials: N
authors.lastname: Nishi
authors.forename: Akira
authors.initials: A
authors.lastname: Yamauchi
authors.forename: Mitsuomi
authors.initials: M
authors.lastname: Hirashima
mesh_terms: D000116:Acetylgalactosamine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001593:Benzyl Compounds / Q000494:pharmacology; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D037161:Galectins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000072597:Hepatitis A Virus Cellular Receptor 2; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology* / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011991:Receptors, Virus / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
chemical_list: D001593:Benzyl Compounds; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D037161:Galectins; C442241:Havcr2 protein, mouse; D000072597:Hepatitis A Virus Cellular Receptor 2; D020381:Interleukin-17; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D015850:Interleukin-6; D011991:Receptors, Virus; D053773:Transforming Growth Factor beta1; C508186:galectin 9, mouse; C080739:benzyl-alpha-N-acetylgalactosamine; D000116:Acetylgalactosamine