Tolerogenic dendritic cells: the ins and outs of outcome.

Recent studies point to an important role for dendritic cells (DCs) in the induction of peripheral tolerance, revealing that the maturation and/or activation state of DCs might be a control point for the induction of peripheral tolerance. Recent progress in our understanding of the mechanisms mediating immune tolerance indicates them to be far more complex than hitherto anticipated. Factors deciding the outcome of vaccination with autologous DCs to prevent and treat diseases with an autoimmune background include maturation state of DCs, their administration route, long-term effects, antigen loading, and in vivo microenvironment. DC vaccination, although promising, is far from standardized. In this review, we discuss the ins and outs of DC-mediated immune tolerance and the need for careful experimental design to unequivocally prove the efficacy and reach the goal of optimized use of DCs in autoimmune diseases.