Interleukin-27 suppresses osteoclastogenesis via induction of interferon-γ

Abstract

Interleukin (IL)-27 is a heterodimeric cytokine that is known to have both stimulatory and inhibitory functions during immune responses. We investigated the effects of IL-27 on arthritis and bone erosion in the murine collagen-induced arthritis (CIA) model. We demonstrate that the inhibitory effect of IL-27 on osteoclastogenesis is associated with interferon-? (IFN-?) production by using an IFN-? knockout mouse model. The IL-27-Fc was injected into both CIA and IFN-?-deficient mice. The effects of IL-27-Fc on osteoclast differentiation were evaluated both in vitro and in vivo. The IL-27-Fc-injected mice showed significantly lower arthritis indices and fewer tartrate-resistant acid-phosphatase-positive osteoclasts in their joint tissues than untreated mice. Interleukin-27 inhibited osteoclastogenesis from bone marrow-derived mononuclear cells in vitro, which was counteracted by the addition of anti-IFN-? antibody. The IL-27-Fc did not affect arthritis in IFN-? knockout mice. Interleukin-27 also suppressed osteoclast differentiation in human and intriguingly, it could promote the expression of IFN-? on priming osteoclasts. These results imply that IL-27 suppressed the generation of CIA and osteoclastogenesis, which were mediated by the induction of IFN-?.