Rheumatoid arthritis (RA) belongs to the most common immune-mediated inflammatory diseases. RA results in an impaired quality of life for patients and high socioeconomic costs for our society. Although autoreactive T cells and B cell-derived autoantibodies have been considered to act as major drivers of this disease, underlying mechanisms that control onset of autoimmunity and inflammation have been incompletely understood. Current therapeutic strategies aim at inhibiting inflammation, but do not allow a curative treatment approach.
Within the current project, we seek to understand the early pathogenesis of RA and to decipher molecular pathways that promote the onset of synovial inflammation. During the present funding period, we could further define the molecular characteristics of autoreactive T cells during the murine model of collagen-induced arthritis and human RA. We have identified a set of T cell-derived cytokines that act on synovial macrophages thereby fostering a priming of the synovial microenvironment and lowering the threshold of autoantibody induced inflammation during early stages of autoimmune arthritis. In addition, we were able to define an alternative set of cytokines that derives from synovial macrophages and which is able to promote resolution of inflammation and restoration of tissue homeostasis.
Our findings might thus help to better understand disease-relevant molecular pathways and to design future treatment strategies that will potentially allow to prevent onset of RA and foster resolution of this otherwise chronic inflammatory disease.
