Effect of serotonin on the differentiation of human monocytes into dendritic cells

The local cytokine environment and presence of stimulatory signals determine whether monocytes acquire dendritic cell (DC) or macrophage characteristics and functions. Because enhanced platelet activation is reported in patients with many allergic disorders, such as atopic dermatitis, platelet-derived factors may influence monocytic differentiation into DC. In this study we examined the effect of serotonin, a prototypic mediator of allergic inflammation released mainly by activated platelets at the inflammatory site, on the granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4-driven differentiation of monocytes into monocyte-derived DC. Monocytes from healthy adult donors were cultured with GM-CSF and IL-4 in the presence or absence of serotonin, and the phenotypes and function of these cells were analysed. In the presence of serotonin, monocytes differentiated into DC with reduced expression of co-stimulatory molecules and CD1a, whereas expression of CD14 was increased. These serotonin-treated DC exhibited significantly reduced stimulatory activity toward allogeneic T cells. However, these cells showed enhanced cytokine-producing capacity, including IL-10 but not IL-12. There was no significant difference between both types of DC in phagocytic activity. Experiments using agonists and antagonists indicated that serotonin 5-hydroxytryptamine (5-HT) induced the alteration of their phenotype and reduction in antigen-presenting capacity were mediated via 5-HTR_1/7. It is therefore suggested that serotonin-driven DC may have a regulatory function in the inflammatory process.