Lessons for the pathogenesis of rheumatoid arthritis acquired from experimental animal models

Youn, Jeehee

Abstract

Rheumatoid arthritis, a common human disease with a prevalence of about 1%, is characterized by inflammatory autoimmune responses. However, the etiopathogenesis of rheumatoid arthritis is still incompletely understood. A variety of experimental animal models has been established to investigate the pathogenesis of rheumatoid arthritis. A collageninduced arthritis model which is one of the most widely used experimental murine models is triggered by T cell responses specific to exogenous type II collagen. These T cells play a pivotal role in shaping inflammatory events in which autoantibodies, proinflammatory mediators, and innate effector cells are involved. Recently, a spontaneous arthritis model named K/BxN has been established. These mice are genetically programmed to exhibit predominance of a T cell population bearing autoantigenspecific T cell receptor molecules. Autoantigenspecific antibodies whose generation is solely dependent on the activity of autoantigen-specific T cells serve as a functional scaffold for the inflammatory events during the distal effector phase. These two models exhibit clinical and immunologic manifestations quite similar to those of rheumatoid arthritis and share a common aspect regarding that development of autoimmunity precede the inflammatory effector phase. However, these two models employ somewhat different effector pathways at the distal end-stage of arthritis. In addition to these two models, other experimental models of rheumatoid arthritis have been developed. These include spanteneous models such as TNF-alpa transgenic mice, IL-1 receptor antagonistdeficient mice and Zap-70 mutation mice, and induced models such as bacterial cell wall- and adjuvant-induced arthritis. The experimental animal models, all together, largely contribute to the improvement of Rheumatology, in terms of both the pathogenesis investigation and therapeutic approach.