The component cells of the inflamed rheumatoid synovial membrane are depicted in innate and adaptive predominant compartments

of the inflammatory response. Pivotal cytokine pathways are depicted in which activation of dendritic cells (DCs), T cells, B cells and macrophages underpins the dysregulated expression of cytokines that in turn drive activation of effector cells, including neutrophils, mast cells, endothelial cells and synovial fibroblasts. The clinical manifestations of such effects are highlighted. Only key cytokines are shown in each domain for relative simplicity; the main text contains more detailed description of the precise role of additional cytokines in these processes. Bidirectional arrows represent a relationship between cells that is influenced by the cytokines listed. The pathways that lead to tissue destruction via osteoclast and chondrocyte activation are detailed in Figs 4,5. APRIL, a proliferation-inducing ligand; BAFF, B-cell activating factor; bFGF, basic fibroblast growth factor; CCL21, CC-chemokine ligand 21; CXCL13, CXCchemokine ligand 13; FcgR, Fc receptor for IgG; IFN, interferon; IL, interleukin; LT, lymphotoxin-; M-CSF, macrophage colony-stimulating factor; PAR2, protease-activated receptor 2; RANKL, receptor activator of nuclear factor-B (RANK) ligand; TGF, transforming growth factor-; TH, T helper; TLR, Toll-like receptor; TNF, tumour-necrosis factor; VEGF, vascular endothelial growth factor.