Differential Activation Profiles of Multiple Transcription Factors During Dendritic Cell Maturation

Immature dendritic cells (DC) at the environmental interfaces, such as the skin, constantly survey the tissue for the emergence of microbial products and pro-inflammatory mediators. Upon recognition of such “danger” signals, they undergo dynamic reprogramming of gene expression and functions, the process known as DC maturation, which plays critical roles in both innate and adaptive immune responses. Although DC have been shown to discriminate different maturation stimuli by expressing stimulus-specific signature genes and unique phenotypic and functional properties, underlying mechanisms for this extraordinary plasticity remain relatively unclear. We hypothesized that DC might activate unique sets of transcription factors (TF) upon sensing different stimuli. To test this hypothesis, we transduced a mouse epidermal-derived DC line XS106 to express the luciferase reporter gene under the control of each of 15 different cis-enhancer elements. The resulting DC panels were then exposed to 14 different microbial, endogenous, environmental, and pharmacological agents that produced unique maturational changes. This approach allowed systematic determination of TF activation profiles in DC. Our results revealed striking diversity, with different classes of stimuli triggering preferential activation of distinct sets of TF. We propose that differential TF usage represents a previously unrecognized mechanism regulating the direction of DC maturation.