Dendritic Cells As Inducers of Peripheral Tolerance

Mechanisms of tolerance initiated in the thymus are indispensable for establishing immune homeostasis, but they may not be sufficient to prevent tissue-specific autoimmune diseases. In the periphery, dendritic cells (DCs) play a crucial tolerogenic role, extending the maintenance of immune homeostasis and blocking autoimmune responses. We review here these essential roles of DCs in orchestrating mechanisms of peripheral T cell tolerance as determined by targeted delivery of defined antigens to DCs in vivo in combination with various genetic modifications of DCs. Further, we discuss how DC functions empowered by specific delivery of T cell antigens could be harnessed for tolerance induction in clinical settings. Peripherally induced T cell tolerance is necessary to extend the maintenance of immune homeostasis and to block autoimmune responses. DCs are key inducers of peripheral tolerance. The tolerogenic functions of DCs can be directed and enhanced by in vivo targeted delivery of defined T cell antigens. The crucial pathways and molecular mechanisms regulating peripheral tolerance are being uncovered by approaches combining methods of in vivo targeted delivery of T cell antigens to DCs and various genetic modifications of DCs. The tolerogenic functions of DCs and their specific mechanisms of tolerance, including the induction of de novo converted peripheral regulatory T cells (pTreg cells), can become a foundation of new immunotherapies.