Dendritic cells from bench to bedside and back.

Dendritic cells (DCs) are the most potent antigen-presenting cells of the immune system. They serve as the sentinels that capture antigens in the periphery, process them into peptides and present these to lymphocytes in lymph nodes. DCs play a key role in regulating immunity. Several DC-subsets exist, including myeloid-DCs (MDCs), plasmacytoid-DCs (PDCs) and Langerhans cells (LC). DCs not only instruct T- and B-lymphocytes, but also activate Natural Killer cells and produce interferons, thus linking the innate and adaptive immune system. Inflammatory-mediators and especially the Toll like receptor (TLR) family of proteins have been shown to play a pivotal role in inducing the immune activation program in DCs. TLRs recognize pathogen-associated-molecular-patterns (PAMPS) like LPS or flagellin and signal to alert immune cells in general, and DC in particular. DC activation, also referred to as DC maturation, thus results in immunity. In contrast, resting DC or DC receiving immune-inhibitory signals, like IL-10 and/or corticosteroids, induce immune tolerance via T cell deletion and induction of suppressive T cells, now termed regulatory T cells. Several mouse models have demonstrated that the immunological outcome is depending on the DC activation state; mature immune-activating DC protect mice from a tumor or pathogen while tolerogenic DC induces tolerance against transplanted tissues. Hence, DC acts at the interface of immunity and peripheral tolerance.