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* Department of Immunology/Microbiology and
Department of Internal Medicine, Section of Rheumatology, and
Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL 60612
IL-27 is the newest member of the cytokine family comprised of IL-12 and IL-23. IL-27 was originally described as a cytokine that along with IL-12 induces the differentiation of naive precursor T cells into Th1 effector cells. This activity has been called into question based on evidence in infectious disease and autoimmune models in which IL-27 is not absolutely required for the generation of IFN-
, and IL-27 plays a regulatory role in controlling inflammation. We have previously reported in proteoglycan-induced arthritis (PGIA), a model of rheumatoid arthritis, that severe arthritis is dependent on the production of IFN-. In this study, we report that IL-27 was expressed in spleen and joint tissues of arthritic mice. We determined the involvement of IL-27 in PGIA by assessing the progression of arthritis in IL-27R–/– mice. Development of arthritis in IL-27R–/– mice was delayed and severity reduced in comparison with IL-27R+/+ littermate controls. Histology confirmed a reduction in joint cellularity, cartilage destruction, and bone erosion. Diminished arthritis was associated with fewer T cells producing IFN- and decreased IFN- secretion overtime. Moreover, the frequency of IL-4- and IL-17-expressing T cells and the production of IL-4 and IL-17 were similar in IL-27R–/– mice and controls. Our results indicate that IL-27 is critically involved in the induction of inflammation in PGIA. IL-27 functions by inducing the differentiation of IFN--producing T cells in vivo that are essential for the development of arthritis.
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 research was supported by National Institutes of Health Grant AR45652 (to A.F. and T.T.G.).
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: EBI3, EBV-induced gene 3; CIA, collagen-induced arthritis; Ct, cycle threshold; EAE, experimental autoimmune encephalomyelitis; PGIA, proteoglycan-induced arthritis; Tg, transgenic; PG, proteoglycan; TCCR, T cell cytokine receptor.
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