Cells of the synovium in rheumatoid arthritis. Dendritic cells

Abstract

Dendritic cells are the major antigen-presenting and antigen-priming cells of the immune system. We review the antigen-presenting and proinflammatory roles played by dendritic cells in the initiation of rheumatoid arthritis (RA) and atherosclerosis, which complicates RA. Various signals that promote the activation of NF-kappaB and the secretion of TNF and IL-1 drive the maturation of dendritic cells to prime self-specific responses, and drive the perpetuation of synovial inflammation. These signals may include genetic factors, infection, cigarette smoking, immunostimulatory DNA and oxidized low-density lipoprotein, with major involvement of autoantibodies. We propose that the pathogenesis of RA and atherosclerosis is intimately linked, with the vascular disease of RA driven by similar and simultaneous triggers to NF-kappaB.

Figure 1

Dendritic cells are important directors of immune responsiveness. (a) Under steady-state conditions, recruitment of resting dendritic cell (DC) precursors into tissues and migration into secondary lymphoid organs occurs constitutively, and may favour tolerance induction. (b) On the other hand, stimulation of DC maturation and activation may initiate T-cell proinflammatory cytokine production, cytotoxic function, and B-cell antibody production.

Figure 2

A model for dendritic cell presentation of citrullinated self-antigenic peptides, and the development of chronic autoimmune inflammatory disease of joint and vascular tissues. anti-CCP, anticyclic citrullinated peptide; DC, dendritic cells; EC, endothelial cells; FDC, follicular dendritic cells; MΦ, macrophages; ox-LDL, oxidized low-density lipoprotein; RF, rheumatoid factor.