Tolerogenic dendritic cell vaccines to treat autoimmune diseases: can the unattainable dream turn into reality?

Autoimmune diseases affect about one in 15 individuals in developed countries and are characterized by a breakdown in immune tolerance. Current therapeutic approaches against destructive immune responses in autoimmune diseases are based on non-specific agents systemically suppressing the function of many immune effector cells. This indiscriminate immunosuppression, however, often causes serious and sometimes life-threatening side effects. Therefore, the need for more specific treatments resulting in lower toxicity and longer-term solutions is high. Because of the established role of dendritic cells (DCs) in maintaining the balance between immunity and tolerance, tolerogenic (tol)DCs might be novel therapeutic targets to prevent undesirable (auto-)immune responses. The idea behind tolDC therapy is that it is a highly targeted, antigen-specific treatment that only affects the auto-reactive inflammatory response. The therapeutic potential of tolDCs has already been proven in experimental animal models of different autoimmune disorders as well as with in vitro experiments using ex vivo generated human tolDCs, thus the challenge remains in bringing tolDC therapy to the clinic, although first clinical trials have been conducted. In this review, we will extensively discuss the use of tolDCs for induction of antigen-specific tolerance in several autoimmune disease settings, from bench to bedside, including currently applied strategies to generate tolDCs as well as technical difficulties and challenges in the field.