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*DEXAMETHASONE
The Journal of Immunology, 1999, 162: 6473-6481.
Copyright © 1999 by The American Association of Immunologists

Glucocorticoids Affect Human Dendritic Cell Differentiation and Maturation1

Lorenzo Piemonti2,*, Paolo Monti*, Paola Allavena{dagger}, Marina Sironi{dagger}, Laura Soldini{ddagger}, Biagio Eugenio Leone§, Carlo Socci* and Valerio Di Carlo*

* Laboratory of Experimental Surgery, Surgical Department, S. Raffaele Scientific Institute, Milan, Italy; {dagger} Department of Immunology and Cell Biology, "Mario Negri" Institute, Milan, Italy; {ddagger} Laboratory of Analysis, San Luigi Centre, S. Raffaele Scientific Institute, Milan, Italy; and § University of Milan, Milan, Italy

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.




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