Dendritic cells--why can they help and hurt us

Dendritic cells (DCs) show a Janus-like functional behavior. They help us by their orchestration of numerous immune responses to defend our body against invading pathogenic micro-organisms and also induce regulatory T cells to inhibit immune reactions against autoantigens as well as diverse harmless environmental antigens. However, DCs can also be of harm to us when misguided by their microenvironment as in allergic and autoimmune diseases or when DCs are targeted and exploited by microbes and cancer cells to evade the immune defense. This huge and diverse functional repertoire of DCs requires complex decision-making processes and the integration of multiple stimulatory and inhibitory signals. Although a given DC type has an extensive functionally plasticity, DCs are heterogeneous and individual DC subtypes are differentially distributed in tissues, express distinct sets of pattern recognition receptors and differ in their capacity to program naive T cells. With the help of transgenic mouse models and selective ablation of individual DC subtypes, we are just at the beginning of understanding the DC system in its complexity. Obtaining a more detailed knowledge of the DC system in mice and men holds strong promise for the successful induction of immunity and tolerance in therapeutic trials. This review presents the recent advances in the understanding of DC biology and discusses why and how DC can help and hurt us.