Involvement of Th17 cells and the effect of anti-IL-6 therapy in autoimmune uveitis

Takeru Yoshimura, Koh Hei Sonoda, Nobuyuki Ohguro, Yoshiyuki Ohsugi, Tatsuro Ishibashi, Daniel J. Cua, Takashi Kobayashi, Hiroki Yoshida, Akihiko Yoshimura

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133 Citations (Scopus)

Abstract

Objectives. Human endogenous uveitis is one of the sight-threatening diseases associated with variety of systemic disorders, such as Behcet's disease and sarcoidosis. Recently, biosynthesized antibodies against inflammatory cytokines have been recognized to be useful to control the regional inflammation. In this study, we focused on the possibility of IL-6-based biological therapies for endogenous uveitis. We initially confirmed the significant increase of several inflammatory soluble factors including IL-6 in the vitreous fluids from refractory/chronic engogenous uveitis patients. Methods. To investigate the role of IL-6 in the formation of refractory ocular inflammation, we used the mouse experimental autoimmune uveitis (EAU) model. Both IL-6 and IL-23 are required for the development of IL-17-producing helper T subset (Th17) from naïve CD4+T cells. Results. In the EAU model, neither IL-6-deficient mice nor IL-23-deficient mice could induce Th17 cells and the EAU score was decreased in these mice in the entire time course. We also confirmed that systemic administration of anti-IL-6 receptor antibody ameliorates EAU by suppressing both systemic and regional Th17 responses. Conclusions. IL-6 is responsible for causing ocular inflammation, and it is, at least partially, due to IL-6-dependent Th17 differentiation. IL-6 may be a target for therapy of refractory endogenous uveitis in humans.

Original languageEnglish
Pages (from-to)347-354
Number of pages8
JournalRheumatology
Volume48
Issue number4
DOIs
Publication statusPublished - 2009 Apr 2

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Keywords

  • Autoimmunity
  • Cytokine
  • Eye
  • IL-6 receptor
  • Th17

ASJC Scopus subject areas

  • Rheumatology
  • Pharmacology (medical)

Cite this

Yoshimura, T., Sonoda, K. H., Ohguro, N., Ohsugi, Y., Ishibashi, T., Cua, D. J., Kobayashi, T., Yoshida, H., & Yoshimura, A. (2009). Involvement of Th17 cells and the effect of anti-IL-6 therapy in autoimmune uveitis. Rheumatology, 48(4), 347-354. https://doi.org/10.1093/rheumatology/ken489