Biological role of CD154 in rheumatoid arthritis and atherosclerosis. Immune cells in circulation infiltrate the synovial cavity, where they participate directly in the pathogenesis of rheumatoid arthritis (RA). CD154 expressed on activated T cells and activated platelets (mCD154) or released as a soluble form (sCD154) interacts with CD40 on synovial cells such as B cells, monocytes/macrophages and synovial fibroblasts, as well as with articular chondrocytes. The resulting CD154-mediated responses include release of cytokines, production of matrix metalloproteinases (MMPs) and upregulation of adhesion molecules, all of which enhance the development of RA. On the contrary, increased levels of sCD154 and mCD154 in the vasculature may also contribute to atherosclerotic events by activating vascular cells and inducing the expression of adhesion molecules and the production of cytokines, chemokines, MMPs, and tissue factor. RF, rheumatoid factor.