Development of proteoglycan-induced arthritis is independent of IL-17

被引:81
作者
Doodes, Paul D. [1 ]
Cao, Yanxia [3 ]
Hamel, Keith M. [1 ]
Wang, Yumei [3 ]
Farkas, Balint [2 ]
Iwakura, Yoichiro [4 ]
Finnegan, Alison [1 ,3 ]
机构
[1] Rush Univ, Med Ctr, Dept Immunol Microbiol, Chicago, IL 60612 USA
[2] Rush Univ, Med Ctr, Dept Orthoped Surg, Chicago, IL 60612 USA
[3] Rush Univ, Med Ctr, Dept Internal Med, Rheumatol Sect, Chicago, IL 60612 USA
[4] Univ Tokyo, Inst Med Sci, Ctr Med Expt, Tokyo, Japan
关键词
D O I
10.4049/jimmunol.181.1.329
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
IL-17 is the hallmark cytokine for the newly identified subset of Th cells, Th17. Th17 cells are important instigators of inflammation in several models of autoimmune disease; in particular, collagen induced arthritis (CIA) and experimental autoimmune encephalomyelitis (EAE), which were previously characterized as Th1-mediated diseases. Although high levels of IFN-gamma are secreted in CIA and EAE, disease is exacerbated in IFN-gamma- or IFN-gamma receptor-deficient mice due to the ability of IFN-gamma to suppress IL-17 secretion. However, in proteoglycan-induced arthritis (PGIA), severe arthritis is dependent on the production of IFN-gamma. We were therefore interested in determining the role of IL-17 in PGIA. We assessed the progression of arthritis in IL-17-deficient (IL-17(-/-)) mice and found the onset and severity of arthritis were equivalent in wild-type (WT) and IL-17(-/-) mice. Despite evidence that IL-17 is involved in neutrophil recruitment, synovial fluid from arthritic joints showed a comparable proportion of Gr1(+) neutrophils in WT and IL-17(-/-) mice. IL-17 is also implicated in bone destruction in autoimmune arthritis, however, histological analysis of the arthritic joints from WT and IL-17(-/-) mice revealed a similar extent of joint cellularity, cartilage destruction, and bone erosion despite significantly reduced RANKL (receptor activator of NK-kappa B ligand) expression. There were only subtle differences between WT and IL-17(-/-) mice in proinflammatory cytokine expression, T cell proliferation, and autoantibody production. These data demonstrate that IL-17 is not absolutely required for autoimmune arthritis and that the production of other proinflammatory mediators is sufficient to compensate for the loss of IL-17 in PGIA.
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页码:329 / 337
页数:9
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