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Okuno, T.* ; Nakatsuji, Y.* ; Moriya, M.* ; Takamatsu, H.* ; Nojima, S.* ; Takegahara, N.* ; Toyofuku, T.* ; Nakagawa, Y.* ; Kang, S.* ; Friedel, R.H. ; Sakoda, S.* ; Kikutani, H.* ; Kumanogoh, A.*

Roles of Sema4D-plexin-B1 interactions in the central nervous system for pathogenesis of experimental autoimmune encephalomyelitis.

J. Immunol. 184, 1499-1506 (2010)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Although semaphorins were-originally identified as axonal guidance molecules during neuronal development, it is emerging that several semaphorins play crucial roles in various phases of immune responses. Sema4D/CD100, a class IV semaphorin, has been shown to be involved in the nervous and immune systems through its receptors plexin-B1 and CD72, respectively. However, the involvement of Sema4D in neuroinflammation still remains unclear. We found that Sema4D promoted inducible NO synthase expression by primary mouse microglia, the effects of which were abolished in plexin-B1-deficient but not in CD72-deficient microglia. In addition, during the development of experimental autoimmune encephalomyelitis (EAE), which was induced by immunization with myelin oligodendrocyte glycoprotein-derived peptides, 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 myelin oligodendrocyte glycoprotein-specific T cells derived from wild-type mice were adoptively transferred into plexin-B1-deficient mice or bone marrow chimera mice with plexin-B1-deficient CNS resident cells, the development of EAE was considerably attenuated. Furthermore, blocking Abs against Sema4D significantly inhibited neuroinflammation during EAE development. Collectively, our findings demonstrate the role of Sema4D-plexin-B1 interactions in the activation of microglia and provide their pathologic significance in neuroinflammation.
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Publication type Article: Journal article
Document type Scientific Article
Keywords NITRIC-OXIDE SYNTHASE; IV SEMAPHORIN CD100; MICROGLIAL CELLS; B-CELL; MULTIPLE-SCLEROSIS; NONREDUNDANT ROLES; INTERFERON-GAMMA; ACTIVATION; CD40; EXPRESSION
ISSN (print) / ISBN 0022-1767
e-ISSN 1550-6606
Journal Journal of Immunology
Quellenangaben Volume: 184, Issue: 3, Pages: 1499-1506 Article Number: , Supplement: ,
Publisher American Association of Immunologists
Publishing Place Bethesda
Reviewing status Peer reviewed
Institute(s) Institute of Developmental Genetics (IDG)