| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2009: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Research Abstract |
Sema4D/CD100, a class IV semaphorin, has been shown to be involved in the nervous and immune systems through its receptors Plexin-Bl and CD72, respectively. However, the involvement of Sema4D in neuroinflammation still remains unclear. We here found that Sema4D promoted inducible nitric oxide synthase (iNOS)-expression by primary mouse microglia, of which effects were abolished in Plexin-B1- but not in CD72-deficient microglia. In addition, during the development of experimental autoimmune encephalomyelitis (EAE), we observed that the expression of Sema4D and Plexin-B1 was induced in infiltrating mononuclear cells and microglia, respectively. Consistent with these expression profiles, when encephalitogenic T-cells derived from wild-type mice were adoptively transferred into Plexin-Bl-deficient mice or bone marrow chimera mice with Plexin-Bl-deficient CNS-resident cells, the development of EAE was considerably attenuated. Furthermore, blocking antibodies against Sema4D significantly inhibited neuroinflammation during EAE-development. Collectively, our findings not only demonstrate the role of Sema4D-Plexin-B1 interactions in the activation of microglia but also provide their pathological significance in neuroinflammation.
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