TY - JOUR
T1 - Involvement of Th17 cells and the effect of anti-IL-6 therapy in autoimmune uveitis
AU - Yoshimura, Takeru
AU - Sonoda, Koh Hei
AU - Ohguro, Nobuyuki
AU - Ohsugi, Yoshiyuki
AU - Ishibashi, Tatsuro
AU - Cua, Daniel J.
AU - Kobayashi, Takashi
AU - Yoshida, Hiroki
AU - Yoshimura, Akihiko
N1 - Funding Information:
Funding: This study was supported by Special Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan, the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (NIBIO), the Takeda Science Foundation, the Kato Memorial Trust for Nambyo Research, the Mitsubishi Pharma Research Foundation, the Naito Foundation, Astellas Foundation for Research on Metabolic Disorders, the Japan Intractable Disease Research Foundation, the Suzuken Memorial Foundation, the Yakult Bioscience Research Foundation and the Princess Takamatsu Cancer Research Fund.
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
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U2 - 10.1093/rheumatology/ken489
DO - 10.1093/rheumatology/ken489
M3 - Article
C2 - 19164426
AN - SCOPUS:63249084553
VL - 48
SP - 347
EP - 354
JO - Rheumatology and Rehabilitation
JF - Rheumatology and Rehabilitation
SN - 1462-0324
IS - 4
ER -