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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.
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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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