IL-6 blockade inhibits the induction of myelin antigen-specific Th17 cells and Th1 cells in experimental autoimmune encephalomyelitis

Satoshi Serada, Minoru Fujimoto, Masahiko Mihara, Nobuo Koike, Yoshiyuki Ohsugi, Shintaro Nomura, Hiroto Yoshida, Teppei Nishikawa, Fumitaka Terabe, Tomoharu Ohkawara, Tsuyoshi Takahashi, Barry Ripley, Akihiro Kimura, Tadamitsu Kishimoto, Tetsuji Naka

Research output: Contribution to journalArticle

219 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)9041-9046
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number26
DOIs
Publication statusPublished - 2008 Jul 1

Fingerprint

Th17 Cells
Th1 Cells
Autoimmune Experimental Encephalomyelitis
Myelin Sheath
Interleukin-6
Antigens
Myelin-Oligodendrocyte Glycoprotein
T-Lymphocytes
Multiple Sclerosis
Interleukin-6 Receptors
Peptides
Groin
Lymph Nodes
Monoclonal Antibodies

Keywords

  • Autoimmunity
  • Multiple sclerosis
  • T cells

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

IL-6 blockade inhibits the induction of myelin antigen-specific Th17 cells and Th1 cells in experimental autoimmune encephalomyelitis. / Serada, Satoshi; Fujimoto, Minoru; Mihara, Masahiko; Koike, Nobuo; Ohsugi, Yoshiyuki; Nomura, Shintaro; Yoshida, Hiroto; Nishikawa, Teppei; Terabe, Fumitaka; Ohkawara, Tomoharu; Takahashi, Tsuyoshi; Ripley, Barry; Kimura, Akihiro; Kishimoto, Tadamitsu; Naka, Tetsuji.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 26, 01.07.2008, p. 9041-9046.

Research output: Contribution to journalArticle

Serada, S, Fujimoto, M, Mihara, M, Koike, N, Ohsugi, Y, Nomura, S, Yoshida, H, Nishikawa, T, Terabe, F, Ohkawara, T, Takahashi, T, Ripley, B, Kimura, A, Kishimoto, T & Naka, T 2008, 'IL-6 blockade inhibits the induction of myelin antigen-specific Th17 cells and Th1 cells in experimental autoimmune encephalomyelitis', Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 26, pp. 9041-9046. https://doi.org/10.1073/pnas.0802218105
Serada, Satoshi ; Fujimoto, Minoru ; Mihara, Masahiko ; Koike, Nobuo ; Ohsugi, Yoshiyuki ; Nomura, Shintaro ; Yoshida, Hiroto ; Nishikawa, Teppei ; Terabe, Fumitaka ; Ohkawara, Tomoharu ; Takahashi, Tsuyoshi ; Ripley, Barry ; Kimura, Akihiro ; Kishimoto, Tadamitsu ; Naka, Tetsuji. / IL-6 blockade inhibits the induction of myelin antigen-specific Th17 cells and Th1 cells in experimental autoimmune encephalomyelitis. In: Proceedings of the National Academy of Sciences of the United States of America. 2008 ; Vol. 105, No. 26. pp. 9041-9046.
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AU - Koike, Nobuo

AU - Ohsugi, Yoshiyuki

AU - Nomura, Shintaro

AU - Yoshida, Hiroto

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AU - Terabe, Fumitaka

AU - Ohkawara, Tomoharu

AU - Takahashi, Tsuyoshi

AU - Ripley, Barry

AU - Kimura, Akihiro

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N2 - 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.

AB - 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.

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