This group's long-term goal is to understand how cardiovascular tissues are targeted for attack in the context of systemic autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. This project focuses on macrophages, a key inflammatory cell type. Although the presence of macrophages in inflamed cardiovascular tissues in patients with these diseases has long been recognized, the tools to dissect their precise role in disease pathogenesis have only recently been developed. The group will employ these powerful new tools to study how macrophages contribute to cardiovascular inflammation in the setting of systemic rheumatic diseases.
The researchers have recently described the occurrence of cardiac valve inflammation in a mouse model of autoimmune arthritis. Valvular carditis in this model is similar to that seen in rheumatic diseases in humans. The cytokine interleukin-17 (IL-17) and immune complexes interacting with activating Fc receptors are critical for carditis to develop. Importantly, macrophages are the predominant inflammatory cell type in this model. Macrophages are characterized broadly as M1 (classical/pro-inflammatory) or M2 (alternative/anti-inflammatory). Preliminary data suggest that both of these populations may contribute to valvular carditis. The researchers will study essential aspects of macrophage biology in this model system: entry into the cardiovascular tissue, activation, and effector function.
The group plans to use their novel animal model system to begin to understand how these molecules and cells interact in vivo to provoke tissue pathology, with specific attention to the cardiac valves. The knowledge gained is expected to lead to new therapies to reduce the cardiovascular morbidity and mortality among patients with rheumatoid arthritis, lupus, and related autoimmune conditions.