Inducing tissue specific tolerance in autoimmune disease with tolerogenic dendritic cells.

Current immunosuppressive therapy acts systemically, causing collateral damage and does not necessarily cope with the cause of rheumatoid arthritis. Tissue specific immune modulation may restore tolerance in patients with autoimmune diseases such as RA, but desires knowledge on relevant target autoantigens. We present the case of type 1 diabetes as prototype autoimmune disease with established autoantigens to set the stage for tissue-specific immune modulation using tolerogenic dendritic cells pulsed with autoantigen in RA. This approach induces autoantigen-specific regulatory T cells that exert their tissue-specific action through a combination of linked suppression and infectious tolerance, introducing a legacy of targeted, localised immune regulation in the proximity of the lesion. Several trials are in progress in RA employing various types of tolerogenic DCs. With knowledge on mode of action and confounding effects of concomitant immunosuppressive therapy, this strategy may provide novel immune intervention that may also prevent RA in high-risk subjects.