| Project/Area Number |
12470139
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Tohoku University |
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Principal Investigator |
ONODERA Hiroshi Graduate school, of medicine, associate professor, 大学院・医学系研究科, 助教授 (20214207)
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| 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)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | myasthenia gravis / thymus / chemokine / multiple sclerosis / homing / 神経免疫疾患 / エオタキシン |
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| 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.
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