Adrenergic modulation of dendritic cells function: Relevance for the immune homeostasis

Dendritic cells (DC) play a key role in determining the appropriate immune response to invading pathogens and tolerance to self antigens. Here I review the evidence that dendritic cell functions may be tuned by the sympathetic nervous system via the local release of norepinephrine. In the presence of antigens or microbial products, such as agonists for Toll-like receptors 2 and 4, norepinephrine inhibits dendritic cell migration, antigen presentation and T-helper cells type 1 priming. This effect, which is mainly mediated by beta-adrenergic receptors in DC and interlukin-10 production, limits potentially damaging reactions and is functional in shaping the appropriate humoral immune response to extracellular pathogens that need antibodies to be neutralized. In addition, the response to contact sensitizers seems to involve a modulation of the local sympathetic activity. Thus, the sympathetic nervous system may play a crucial role in modulating DC function during the innate phase of the immune response. This evidence has many pathophysiological implications and offers new tools for modulating the immune response.