(p40)2-Fc reduces immune-inflammatory response through the activation of T cells in collagen induced arthritis mice

Abstract

IL-12p40 homodimer, a natural antagonist of IL-12 and IL-23, performs an important role in the expression of proinflammatory cytokines that is essential for Th1 and Th17 immune responses. Here, we reveal the therapeutic and immunosuppressive effect of the IL-12p40 subunit ((p40)(2)-Fc) in an experimental autoimmune arthritis model. We hypothesized that (p40)(2)-Fc may reduce the inflammatory response and the activation of T cells. In this study, we intraperitoneally injected (p40)(2)-Fc into collagen induced arthritis (CIA) mice to identify whether (p40)(2)-Fc attenuates CIA severity. (p40)(2)-Fc reduced the development of CIA, joint inflammation and cartilage destruction. (p40)(2)-Fc also significantly decreased the concentration of serum immunoglobulin as well as the number of T cells and C II specific T cells. In addition, osteoclastogenesis in (p40)(2)-Fc treated mice was down-regulated compared to the mice treated with (p40)(2)-Fc control. We observed that (p40)(2)-Fc treatment alleviates arthritis in mice with CIA, reducing inflammation and osteoclast differentiation. These findings suggest that (p40)(2)-Fc can be a potential therapeutic approach for autoimmune arthritis. (C) 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.