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2002 Fiscal Year Final Research Report Summary

Chemokine signaling in myasthenia gravis and multiple sclerosis

Research Project

Project/Area Number 12470139
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionTohoku University

Principal Investigator

ONODERA Hiroshi  Graduate school, of medicine, associate professor, 大学院・医学系研究科, 助教授 (20214207)

Co-Investigator(Kenkyū-buntansha) FUJIHARA Kazuo  Graduate school of medicine, associate professor, 医学部附属病院, 助教授 (70280873)
ITOYAMA Yasuto  Graduate school of medicine, professor, 大学院・医学系研究科, 教授 (30136428)
YOSHIE Osamu  Kinki University, School of medicine, Professor, 医学部, 教授 (10166910)
Project Period (FY) 2000 – 2002
Keywordsmyasthenia gravis / thymus / chemokine / multiple sclerosis / homing
Research Abstract

We studied chemokine signaling in lymphocytes of patients with myasthenia gravis and multiple sclerosis. Th1-type chemokine signaling in peripheral blood CD4+ T cells was significantly altered in myasthenia gravis patients with thymoma, while both Th1-and Th2-type chemokine signaling were altered in patients with hyperplasic thymus. The mRNA level for chemokine CCL21 was selectively increased in the hyperplasic thymuses, and cellular migration by CCL21 was markedly enhanced in thymocytes obtained from hyperplasic thymuses but not from normal thymuses or thymomas. The expression of another CCR7 ligand named CCL19 was similar among normal thymuses, hyperplasic thymuses, and thymomas. Since CCL21 plays a critical role in the homing of lymphocytes and dendritic cells to lymphoid organs and B cells activation, the elevated CCL21 expression in hyperplasic thymuses is causatively associated with the immune abnormalities of myasthenia gravis patients with thymic hyperplasia. Th1-type chemokine receptor expression on cerebrospinal fluid (CSF) T cells were significantly elevated in multiple sclerosis patients. The number of CD4+ T cells with CCR5 in CSF was transiently increased at relapse stage. In contrast, the number of CD4+ T cells with another Th1-type receptor CXCR3 remained high in the CSF obtained both at relapse stage and remission stage. These data suggest that modulation of chemokine signaling is a promising method to treat patients with myasthenia gravis and multiple sclerosis.

  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] Misu T, Oncdera H, et al.: "Chemokine receptor expression on T cells in blood and cerebrospinal fluid at relapse and remission of multiple sclerosis"J. Neuroimmunology. 114. 207-212 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nagata T, Onodera H, et al.: "Decreased expression of c-myc genes in thymuses from myasthenia gravis patients"J. Neuroimmunology. 115. 199-202 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tsuda T, Onodera H, et al.: "Impaired chemosensitivity of hypoxia is a marker of multiple system atrophy"Annals of Neurology. 52. 367-371 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Onodera H. et al.: "Effect of 10-T static magnetic field on human peripheral blood immune cells"Radiation Research. (in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mitu T, Onodera H, Fujihara K, Matsushima K, Yoshie O, Okita N, Takase S, Itoyama Y: "Chemokine receptor expression on T cells in blood and cerebrospinal fluid at relapse and remission of multiple sclerosis: imbalance of Th1/Th2-associated chemokine signaling"J Neuroimmunol. 114. 207-12 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nagata T, Onodera H, Ohuchi M, Suzuki Y, Tago H, Fujihara K, Ishii N, Sugamura K, Shoji Y, Handa M, Tabayashi K, Itoyama Y: "Decreased expression of c-myc family genes in thymuses from myasthenia gravis patients"J Neuroimmunol. 115. 199-202 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsuda T, Onodera H, Okabe S, Kikuchi Y, Itoyama Y: "Impaired chemosensitivity to hypoxia is a marker of multiple system atrophy"Ann Neurol. 52. 367-71 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Onodera H, Jin Z, Chida S, Suzuki Y, Tago H, Itoyama Y: "Effects of 10-Tesia static magnetic field on human peripheral blood immune cells"Radiation Research. (in press). (2003)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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