title: IL-6 blockade inhibits the induction of myelin antigen-specific Th17 cells and Th1 cells in experimental autoimmune encephalomyelitis.
abstract: The development of Th17 cells is a key event in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a murine model of human multiple sclerosis (MS). Previous studies have demonstrated that an IL-6-dependent pathway is involved in the differentiation of Th17 cells from naïve CD4-positive T cells in vitro. However, the role of IL-6 in vivo in the development of Th17 cells in EAE has remained unclear. In the present study, we found that IL-6 blockade by treatment with an anti-IL-6 receptor monoclonal antibody (anti-IL-6R mAb) inhibited the development of EAE and inhibited the induction of myelin oligodendrocyte glycoprotein (MOG) peptide-specific CD4-positive, CD8-positive, and Th17 T cells, in inguinal lymph nodes. Thus, the protective effect of IL-6 blockade in EAE is likely to be mediated via the inhibition of the development of MOG-peptide-specific Th17 cells and Th1 cells, which in turn leads to reduced infiltration of T cells into the CNS. These findings indicate that anti-IL-6R mAb treatment might represent a novel therapy for human MS.
authors.affiliation: Laboratory for Immune Signal, National Institute of Biomedical Innovation, 7-6-8 Saito-asagi, Ibaraki, Osaka 565-0085, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Serada
authors.forename: Minoru
authors.initials: M
authors.lastname: Fujimoto
authors.forename: Masahiko
authors.initials: M
authors.lastname: Mihara
authors.forename: Nobuo
authors.initials: N
authors.lastname: Koike
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Ohsugi
authors.forename: Shintaro
authors.initials: S
authors.lastname: Nomura
authors.forename: Hiroto
authors.initials: H
authors.lastname: Yoshida
authors.forename: Teppei
authors.initials: T
authors.lastname: Nishikawa
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Terabe
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Ohkawara
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Takahashi
authors.forename: Barry
authors.initials: B
authors.lastname: Ripley
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kimura
authors.forename: Tadamitsu
authors.initials: T
authors.lastname: Kishimoto
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Naka
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000941:Antigens / Q000276:immunology*; D002465:Cell Movement; D002490:Central Nervous System / Q000276:immunology / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D000939:Epitopes / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008221:Lymphoid Tissue / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009185:Myelin Proteins; D009186:Myelin Sheath / Q000276:immunology*; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D010455:Peptides / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000941:Antigens; D000939:Epitopes; D015850:Interleukin-6; C571326:MOG protein, human; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010455:Peptides