title: Chondroitin 6-O-sulfate ameliorates experimental autoimmune encephalomyelitis.
abstract: Chondroitin sulfate proteoglycans (CSPGs) are the main component of the extracellular matrix in the central nervous system (CNS) and influence neuroplasticity. Although CSPG is considered an inhibitory factor for nerve repair in spinal cord injury, it is unclear whether CSPG influences the pathogenetic mechanisms of neuroimmunological diseases. We induced experimental autoimmune encephalomyelitis (EAE) in chondroitin 6-O-sulfate transferase 1-deficient (C6st1(-/-)) mice. C6ST1 is the enzyme that transfers sulfate residues to position 6 of N-acetylgalactosamine in the sugar chain of CSPG. The phenotypes of EAE in C6st1(-/-) mice were more severe than those in wild-type (WT) mice were. In adoptive-transfer EAE, in which antigen-reactive T cells from WT mice were transferred to C6st1(-/-) and WT mice, phenotypes were significantly more severe in C6st1(-/-) than in WT mice. The recall response of antigen-reactive T cells was not significantly different among the groups. Furthermore, the number of pathogenic T cells within the CNS was also not considerably different. When EAE was induced in C6ST1 transgenic mice with C6ST1 overexpression, the mice showed considerably milder symptoms compared with those in WT mice. In conclusion, the presence of sulfate at position 6 of N-acetylgalactosamine of CSPG may influence the effecter phase of EAE to prevent the progression of pathogenesis. Thus, modification of the carbohydrate residue of CSPG may be a novel therapeutic strategy for neuroimmunological diseases such as multiple sclerosis.
authors.affiliation: Department of Neurology, Kinki University School of Medicine, Osaka-Sayama, Japan.
authors.forename: Katsuichi
authors.initials: K
authors.lastname: Miyamoto
authors.forename: Noriko
authors.initials: N
authors.lastname: Tanaka
authors.forename: Kota
authors.initials: K
authors.lastname: Moriguchi
authors.forename: Rino
authors.initials: R
authors.lastname: Ueno
authors.forename: Kenji
authors.initials: K
authors.lastname: Kadomatsu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kitagawa
authors.forename: Susumu
authors.initials: S
authors.lastname: Kusunoki
mesh_terms: D000117:Acetylglucosamine / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000818:Animals; D002809:Chondroitin Sulfates / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015238:Sulfotransferases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000097811:Carbohydrate Sulfotransferases
chemical_list: D000117:Acetylglucosamine; D002809:Chondroitin Sulfates; D015238:Sulfotransferases; D000097811:Carbohydrate Sulfotransferases
keywords: central nervous system; chondroitin sulfate; experimental autoimmune encephalomyelitis; multiple sclerosis; myelin oligodendrocyte glycoprotein; proteoglycan