title: Roles of Sema4D-plexin-B1 interactions in the central nervous system for pathogenesis of experimental autoimmune encephalomyelitis.
abstract: 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.
authors.affiliation: Department of Immunopathology, Osaka University Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Tatsusada
authors.initials: T
authors.lastname: Okuno
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nakatsuji
authors.forename: Masayuki
authors.initials: M
authors.lastname: Moriya
authors.forename: Hyota
authors.initials: H
authors.lastname: Takamatsu
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nojima
authors.forename: Noriko
authors.initials: N
authors.lastname: Takegahara
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Toyofuku
authors.forename: Yukinobu
authors.initials: Y
authors.lastname: Nakagawa
authors.forename: Sujin
authors.initials: S
authors.lastname: Kang
authors.forename: Roland H
authors.initials: RH
authors.lastname: Friedel
authors.forename: Saburo
authors.initials: S
authors.lastname: Sakoda
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kikutani
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kumanogoh
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001854:Bone Marrow Cells / Q000201:enzymology / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D011828:Radiation Chimera / Q000276:immunology; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D039961:Semaphorins / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
chemical_list: D009419:Nerve Tissue Proteins; C492118:Plxnb1 protein, mouse; D011956:Receptors, Cell Surface; C103150:Sema4d protein, mouse; D039961:Semaphorins