Glucocorticoids affect human dendritic cell differentiation and maturation

Because dendritic cells (DC) play a major role in the initiation of T cell- mediated immunity, we studied the effects of glucocorticoids, well-known in hibitors of the immune and inflammatory response, on the differentiation an d maturation of human DC. DC were differentiated from human monocytes by cu lture with GM-CSF and IL-4 for 7 days with and without dexamethasone (Dex), Cells treated with Dex (10(-8) M) (Dex-DC) developed a characteristic dend ritic morphology; however, membrane phenotype analysis demonstrated that th ey were not fully differentiated, Dex-DC expressed low levels of CD1a and, unlike untreated cells, high levels of CD14 and CD16, Molecules involved in Ag presentation (CD40, CD86, CD54) were also impaired. In contrast, molecu les involved in Ag uptake (mannose receptor, CD32) and cell adhesion (CD11/ CD18, CD54) were up-regulated. After exposure to TNF-alpha or CD40 ligand, Dex-DC expressed lower levels of CD83 and CD86 than untreated cells, Dex-DC showed a higher endocytic activity, a lower APC function, and a lower capa city to secrete cytokines than untreated cells. Overall, these results indi cate that DC differentiated in the presence of Dex are at a more immature s tage. Moreover, Dex also partially blocked terminal maturation of already d ifferentiated DC, In conclusion, our data suggest that glucocorticoids may act at the very first step Of the immune response by modulating DC differen tiation, maturation, and function.