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 inhibitors of the immune and inflammatory response, on the differentiation and maturation of human DC. DC were differentiated from human monocytes by culture 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 dendritic morphology; however, membrane phenotype analysis demonstrated that they 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, molecules 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 capacity to secrete cytokines than untreated cells. Overall, these results indicate that DC differentiated in the presence of Dex are at a more immature stage. Moreover, Dex also partially blocked terminal maturation of already differentiated DC. In conclusion, our data suggest that glucocorticoids may act at the very first step of the immune response by modulating DC differentiation, maturation, and function.
Piemonti
L
L
Laboratory of Experimental Surgery, Surgical Department, S. Raffaele Scientific Institute, Milan, Italy. lorenzo.piemonti@hsr.it
Monti
P
P
Allavena
P
P
Sironi
M
M
Soldini
L
L
Leone
B E
BE
Socci
C
C
Di Carlo
V
V
D017951:Antigen Presentation / Q000187:drug effects; D019013:CD40 Antigens / Q000378:metabolism; D023201:CD40 Ligand; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D037181:Lectins, C-Type; D008024:Ligands; D008358:Mannose / Q000378:metabolism; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D008562:Membrane Glycoproteins / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D010873:Pinocytosis / Q000187:drug effects / Q000276:immunology; D011956:Receptors, Cell Surface / Q000502:physiology; D012995:Solubility; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D019013:CD40 Antigens; D016207:Cytokines; D006131:Growth Inhibitors; D007166:Immunosuppressive Agents; D037181:Lectins, C-Type; D008024:Ligands; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand; D003907:Dexamethasone; D008358:Mannose