Global reprogramming of dendritic cells in response to a concerted action of inflammatory mediators.

Maturation of dendritic cells (DC) serves a deterministic role in the link between innate and adaptive immunity, constituting a checkpoint with regard to whether responses from the lymphocyte compartment shall be raised and what class of response is needed to protect the host against invading pathogens. Since DC have not been shown to possess mechanisms such as gene recombination or somatic mutation for generating a diverse repertoire of antigen-recognition receptors, it is unlikely that these leukocytes can intrinsically respond to all conceivable molecules present in our environment. In the present study, we have therefore determined how mediators of the inflammatory response regulate global gene transcription in DC. The data represent an extensive and time-ordered reprogramming of the DC during their course of maturation, involving genes encoding proteins that regulate responses of both innate cells and lymphocytes. This transcriptional reorganization may reflect the effect of in vivo released inflammatory mediators induced by endogenous or pathogenic stimulation.