Figure 1

Immune pathways in rheumatoid arthritis. Innate and adaptive immune pathways integrate to promote inflammation and tissue damage. The interactions among dendritic cells, T cells and B cells occur primarily in the lymph node and generate both the autoimmune response and the activation of T cells. Upon stimulation by T cells, activated B cells differentiate into memory B cells and plasma cells producing autoantibodies such as RF and ACPA. B cells secrete pro-inflammatory cytokines and lymphotoxin (LT)-α that enhance inflammation and synovial lymphoneogenesis. In the synovial membrane, cell-contact interactions among T cells, natural killer cells, synovial fibroblasts, macrophages and osteoclasts generate positive feedback loops mediated by cytokines, chemokines, matrix metalloproteases (MMPs) and cathepsins that drive the chronic phase of the disease inducing tissue remodelling and damage. BCR, B cell receptor; TCR, T cell receptor; MHC, major histocompatibility complex