Application of glycolipid treatment for multiple sclerosis

2003 Fiscal Year Final Research Report Summary

• Project/Area Number: 14370214
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: YAMAMURA Takashi National Center of Neurology and Psychiatry (NCNP), National Institute of Neuroscience, Department of Immunology, Director, 神経研究所・疾病研究第六部, 部長 (90231670)
• Co-Investigator(Kenkyū-buntansha): MIYAKE Sachiko National Center of Neurology and Psychiatry (NCNP), National Institute of Neuroscience, Department of Immunology, Section Chief, 神経研究所・免疫研究部, 室長 (50266045)
• Project Period (FY): 2002 – 2003
• Keywords: multiple sclerosis / neuroimmunology / NKT cell / OCH / alpha-galactosylceramide / cytokine / immunomodulatoration / Th1 / Th2

Research Abstract

This group of investigators has already clarified that a glycolipid compound referred to as OCH, that is stimulatory for NKT cells, could inhibit the development of the animal model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE) by inducing Th2 bias of autoimmune T cells. The purpose of the study was to evaluate if OCH treatment could be also effective for modulating Th1/Th2 balance in human MS. To do so, we have generated a number of NKT cell clones from peripheral blood the patients with MS and healthy individuals. The clones were classified into CD4-positive (CD4+) and CD4-negative (CD4-). CD4-clones responded strongly to alpha-galactosylceramide (alpha-GC), a prototype ligand for NKT cells, but did not so in response to OCH. By contrast, CD4+ clones responded to both OCH and alpha-GC. Interestingly, OCH stimulation was relatively more effective than alpha-GC stimulation in inducing Th2 cytokines. These results support that OCH may be applicable for treatment of MS in the future.

Research Products

• [Publications] Satoh J-i et al.: "The 14-3-3 protein epsilon isoform expressed in reactive astrocytes in demyelinating lesions of multiple sclerosis binds to vimentin and glial fibrillary acidic protein in cultured human astrocytes"Am.J.Pathol.. 印刷中.
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Takahashi K et al.: "The regulatory role for natural killer cells in maltiple sclerosis"Brain. 印刷中.
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Oki S et al.T: "The clinical implication and molecular mechanism of preferential IL-4 production by modified glycolipid-stimulated NKT cells"J.Clin.Invest.. 印刷中.
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Illes Zs et al.: "Accumulation of Vα7.2-Jα33 invariant T cells in human autoimmune inflammatory lesions in the nervous system."Int.Immunol.. 16. 223-230 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Bedoui S et al.: "Neuropeptide Y (NPY) suppresses experimental autoimmune encephalomyelitis : NPY_1 receptor-specific inhibition of autoreactive Th1 responses in vivo."J.Immunol.. 171. 3451-3458 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Koike F et al.: "Microarray analysis identifies IFNβ-regulated genes in multiple sclerosis"J.Neuroimmunol.. 139. 109-118 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] 山村 隆, 三宅 幸子: "免疫2004"中山書店. 305-311 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Satoh, J-i., T.Yamamura, K.Arima: "The 14-3-3 protein epsilon isoform, expressed in reactive astrocytes in demyelinating lesions of multiple sclerosis, binds to vimentin and glial fibrillary acidic protein in cultured human astrocytes."Am J Pathol. (in press). (2004)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Takahashi, K., S.Miyake, M.Endoh, T.Yamamura: "The regulatory role for natural killer cells in multiple sclerosis"Brain. (in press). (2004)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Oki, S., A.Chiba, T.Yamamura, S.Miyake: "The clinical implication and molecular mechanism of preferential IL-4 production by modified glycolipid-stimulated NKT cells"J.Clin.Invest.. (in press). (2004)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Illes, Zs., M.Shimamura, J.Newcombe, N.Oka, T.Yamamura: "Accumulation of Vα7.2-Jα33 invariant T cells in human autoimmune inflammatory lesions in the nervous system."Int.Immunol.. 16. 223-230 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Bedoui, S., S.Miyake, Y.Lin, K.Miyamoto, S.Oki, N.Kawamura, A.Beck-Sickinger, S.von Hoersten, T.Yamamura: "Neuropeptide Y (NPY) suppresses experimental autoimmune encephalomyelitis : NPY_1 receptor-specific inhibition of autoreactive Th1 responses in vivo"J.Immunol.. 171. 3451-3458 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Koike, F., J-i.Satoh, S.Miyake, T.Yamamoto, M.Kawai, S.Kikuchi, K.Nomnura, K.Yokoyama, K.Ota, T.Kanda, T.Fukazawa, T.Yamamura: "Microarray analysis identifies IFNβ-regulated genes in multiple sclerosis"J.Neuroimmunol.. 139. 109-118 (2003)
  • Description: 「研究成果報告書概要(欧文)」より