Chondroitin 6-O-sulfate ameliorates experimental autoimmune encephalomyelitis

Chondroitin sulfate proteoglycans (CSPGs) are the main component of the extracellular matrix in the central nervous system (CNS) and influences 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 mice were. In adoptive-transfer EAE, in which antigen-reactive T cells from wild-type mice were transferred to C6st1 and wild-type mice, phenotypes were significantly more severe in C6st1 than in wild-type 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 wild-type 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,