Keratan sulfate exacerbates experimental autoimmune encephalomyelitis

J Neurosci Res. 2015 Dec;93(12):1874-80. doi: 10.1002/jnr.23640. Epub 2015 Sep 5.

Abstract

Proteoglycans (PGs) are the components of extracellular matrices in the central nervous system (CNS). Keratan sulfate (KS) is a glycosaminoglycan that is included in the KSPG that acts as an inhibitory factor in nerve regeneration after CNS injury. To investigate the role of KS in immune diseases, we induced experimental autoimmune encephalomyelitis (EAE) in mice that were deficient in the N-acetylglucosamine (GlcNAc)-6-O-sulfotransferase 1 (GlcNAc6ST1) gene (KS-KO). KS-KO mice developed less severe EAE and showed repressed recall response in the induction phase. Furthermore, GlcNAc6ST1 might have roles in the passage of the pathogenic lymphocytes through the blood-brain barrier via adhesion molecules. Thus, modulation of KS may become a treatment for neuroimmunological diseases.

Keywords: central nervous system; experimental autoimmune encephalomyelitis; glycosaminoglycan; keratan sulfate; multiple sclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer / adverse effects
  • Animals
  • Carbohydrate Sulfotransferases
  • Cell Proliferation / drug effects
  • Cytokines / metabolism
  • Disease Models, Animal
  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • Encephalomyelitis, Autoimmune, Experimental / chemically induced*
  • Encephalomyelitis, Autoimmune, Experimental / genetics*
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Freund's Adjuvant / toxicity
  • Keratan Sulfate / toxicity*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myelin-Oligodendrocyte Glycoprotein / toxicity
  • Peptide Fragments / toxicity
  • Sulfotransferases / deficiency
  • Sulfotransferases / genetics
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / pathology

Substances

  • Cytokines
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments
  • myelin oligodendrocyte glycoprotein (35-55)
  • Freund's Adjuvant
  • Keratan Sulfate
  • Sulfotransferases