Activated T cells and monocytes/macrophages play a central role in the joint inflammation and tissue destruction in rheumatoid arthritis by cell contact and by the production of soluble mediators such as cytokines, enzymes and oxygen metabolites. The synovial infiltrates are characterized by high numbers of these cells. Animal in vivo models and human in vitro / ex vivo models of arthritis support that T cells and macrophages are important in regulation of inflammation and tissue destruction. Counteracting T cell and macrophage activity at different levels results in inhibition of artritis in these experimental models and in clinical studies.
In our studies we focus on the disregulations of the interaction between T cells and macrophages in the early and chronic phase of the arthritis. In these phases this dysregulation is expected to be of greater importance than antigen dependency and genetic predisposition. Studying the interaction we concentrate on the distinctive disregulation in production of and response to soluble mediators as well as a disturbed response of the cells in direct cell-cell contact. By specific inhibition of the harmful immune activity and/or supporting a proper immune response, the imbalance might be broken and normalised, maybe even for a prolonged (infinite) period of time.
For more information contact Dr Joel van Roon (email: J.A.G.vanRoon@umcutrecht.nl)