Dendritic cells as targets for therapy in rheumatoid arthritis.

Abstract

Dendritic cells (DCs) are central in inducing immunity and in mediating immune tolerance in their role as professional antigen-presenting cells. In the absence of DCs, a fatal autoimmunity develops in animal models. Although the role of DCs has been investigated extensively in the pathogenesis of rheumatoid arthritis (RA), it remains unclear whether DCs initiate autoimmunity in this disease. Nevertheless, evidence points towards a significant role for DCs in disease maintenance and progression. Current biologic therapies target cytokine products of antigen-presenting cells, such as tumor necrosis factor, interleukin-1 and interleukin-6. Emerging therapies for RA exploit the tolerogenic capacity of DCs. 'Tolerogenic' DCs can be generated from myeloid precursors ex vivo, loaded with antigen, and manipulated to suppress autoimmune responses in vivo, through the induction of activation-induced cell death, anergy, and/or regulatory T cells. Cells that are primed by DCs, such as B cells, type 1 and type 17 T helper cells, and that have been implicated in certain models of autoimmunity, are also being considered as additional targets for immune-based therapy. Studies to validate these approaches to ameliorate autoimmunity will be necessary before their application in the clinic.