Chemokines and leukocyte trafficking in rheumatoid arthritis

Leukocyte infiltration into the joint space and tissues is an essential component of the pathogenesis of rheumatoid arthritis (RA). In this review, we will summarize the current understanding of the mechanisms of leukocyte trafficking into the synovium, focusing on the role of adhesion molecules, chemokines, and chemokine receptors in synovial autoimmune inflammation. The process by which a circulating leukocyte decides to migrate into the synovium is highly regulated and involves the capture, firm adhesion, and transmigration of cells across the endothelial monolayer. Adhesion molecules and chemokine signals function in concert to mediate this process and to organize leukocytes into distinct structures within the synovium. Chemokines play a key regulatory role in organ-specific leukocyte trafficking and activation by affecting integrin activation, chemotaxis, effector cell function, and cell survival. Consequently, chemokines, their receptors, and downstream signal transduction molecules are attractive therapeutic targets for RA.