IL-6 blockade inhibits the induction of myelin antigen-specific Th17 cells and Th1 cells in experimental autoimmune encephalomyelitis.
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.
Serada
Satoshi
S
Laboratory for Immune Signal, National Institute of Biomedical Innovation, 7-6-8 Saito-asagi, Ibaraki, Osaka 565-0085, Japan.
Fujimoto
Minoru
M
Mihara
Masahiko
M
Koike
Nobuo
N
Ohsugi
Yoshiyuki
Y
Nomura
Shintaro
S
Yoshida
Hiroto
H
Nishikawa
Teppei
T
Terabe
Fumitaka
F
Ohkawara
Tomoharu
T
Takahashi
Tsuyoshi
T
Ripley
Barry
B
Kimura
Akihiro
A
Kishimoto
Tadamitsu
T
Naka
Tetsuji
T
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*
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