Dendritic cells as precursors of osteoclasts

Dendritic cells (DCs) play an important role in bridging the innate and the adaptive immune response by serving as antigen presenting cells and are therefore important in initiating an adaptive immune response due to their capacity to activate nave T cells. DCs themselves are cells of the innate immune system, as are monocytes, macrophages and osteoclasts. DCs have been demonstrated to be present locally in the inflamed joint of patients suffering from rheumatoid arthritis, but it is not clear what role they play there in inflammatory arthritis. It is known, however, that bone degrading osteoclasts can derive from DCs under certain conditions in vitro. By using murine models of inflammatory arthritis in combination with genetically engineered mice in which DCs can specifically depleted, we will be able to dissect the contribution of DCs in the pathogenesis of arthritis. These experiments will clarify whether DCs, in addition of initiating autoimmunity, also are important in the maintenance of inflammatory arthritis, are involved either directly or indirectly in inflammatory joint destruction and ultimately, whether they would represent a suitable target for therapeutic intervention.