Dendritic cells in rheumatoid arthritis.

Dendritic cells are the most potent subset of antigen presenting cells. They are derived from bone marrow stem cells and reside in peripheral tissues or blood. Upon exposure to antigens and cytokines the peripheral DC s, express high amounts of peptide-MHC, and upregulate their costimulatory molecules, migrate to draining lymph nodes, and interact with T cells to stimulate or tolerize them. Dendritic cells have been found in synovium and joint fluid in rheumatoid arthritis, often at the center of a cluster of T cells. These DC s express MHC II, the costimulatory molecules CD40, CD80, CD86, adhesion molecules such as DC-SIGN and chemokine receptors such as CCR7. DC s can polarize T cells into Th1 or Th2 phenotypes depending on the cytokine environment. Th1 responses are initiated in context of IL-12 and IL-23. The cytokine milieu of the RA synovium promotes DC differentiation and function that could lead to autoantigen presentation to T cells. Dendritic cells may be central to the pathogenesis of RA and could also be logical targets for treatment. DC s themselves could be used to deliver therapeutic gene products in autoimmune disease. DC s genetically modified to express IL-4 have been used to treat or prevent collagen arthritis in mice.