Dendritic cells in networks of immunological tolerance

Dendritic cells (DC) represent pacemakers of the immune system because they play a major role as antigen-presenting cells in inducing adaptive immune responses on the one hand and are critically involved in promoting and maintaining immunological tolerance on the other. The latter function is mediated by specialized subsets of DC, named tolerogenic DC, as well as by DC activated or differentiated in the presence of specific biological or chemical agents. Suppression by tolerogenic DC is primarily mediated via the induction of regulatory T (Tr) cells. In the present review, we will focus on human tolerogenic DC with the aim to: (1) describe subsets of human tolerogenic DC; (2) define the modes of in vitro induction of myeloid tolerogenic DC and their ability to induce Tr cells; (3) elucidate the role of tolerogenic DC in orchestrating tolerance induction in vivo; and (4) envisage the use of tolerogenic DC as therapeutic tool to trigger immunoregulatory mechanisms.