The global transcriptional maturation program and stimuli-specific gene expression profiles of human myeloid dendritic cells.

Abstract

Dendritic cells (DC) are central to the immune response against invading pathogens. How DC translate different signals received from either other components of the immune system or from pathogens into a tailored immune response is not understood in detail. Using oligonucleotide microarray technology we performed a genome-wide analysis to investigate the transcriptional program in immature human monocyte-derived DC induced to mature with either CD40 ligand (CD40L), lipopolysaccharide (LPS) or a cocktail of inflammatory cytokines and prostaglandin (PG) E(2) (CyC). We identified elements of a sustained common response to LPS and CyC, as well as sets of transient and stimulus-specific gene expression changes. Interestingly, the transient LPS response as well as the sustained LPS-specific response included a high number of chemokines, suggesting that LPS stimulation of DC leads to enhanced recruitment of immune cells and potentially prolongs the immune response compared to an inflammatory signal mimicked by CyC. Of note, the core response common to both LPS and CyC comprised a high number of unknown genes as well as genes that have not been previously identified as part of the maturation response in DC. Since some of these genes have down-regulatory functions in other settings, they may have a regulatory role in DC maturation and immune response generation.