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* Department of Immunology/Microbiology,
Department of Orthopedic Surgery, and
Department of Internal Medicine, Section of Rheumatology, Rush University Medical Center, Chicago, IL 60612; and
Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan
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-
are secreted in CIA and EAE, disease is exacerbated in IFN-- or IFN- receptor-deficient mice due to the ability of IFN- to suppress IL-17 secretion. However, in proteoglycan-induced arthritis (PGIA), severe arthritis is dependent on the production of IFN-. 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-
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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institutes of Health Grant AR47652 (to A.F.).
2 Address correspondence and reprint requests to Dr. Alison Finnegan, Department of Medicine, Section of Rheumatology, Rush University Medical Center, 1735 West Harrison Avenue, Chicago, IL 60612. E-mail address: Alison_Finnegan{at}rush.edu
3 Abbreviations used in this paper: RA, rheumatoid arthritis; CIA, collagen-induced arthritis; EAE, experimental autoimmune disease; PG, human proteoglycan (aggrecan); PGIA, PG-induced arthritis; qRT-PCR, quantitative RT-PCR; RANKL, receptor activator of NK-B; WT, wild type.
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