Figure 2

Role of chemokines in the migration of DCs and T-cell subsets in RA synovitis. In response to local inflammation and production of proinflammatory cytokines, after an unknown event CC chemokine receptor (CCR)6⁺ immature dendritic cells (DCs) and T-helper (Th)17 cells are attracted to the synovium in response to local production of CC chemokine ligand (CCL)20 in the perivascular infiltrates and the lining layer. It is also possible that CCR6⁺ cells migrate to the synovial fluid toward CCL20 expressed within the lining layer. The presence of mature DCs in synovium results from the combined effects of cell interactions and cytokine microenvironment. Defects in production of differentiation factors such as IL-4 may favor a relative accumulation of immature DCs. However, detection of CCL19 and CCL21 in perivascular infiltrates and vascular endothelium argues for a direct migration of some CCR7⁺ mature DCs from blood into the synovium, where they can interact with lymphocytes, leading to potent local activation. RA, rheumatoid arthritis.