Glucocorticoids increase the endocytic activity of human dendritic cells.
We have investigated the effect of glucocorticoids (GC) on antigen uptake molecule expression and on endocytic activity of human dendritic cells (DC). Human monocyte-derived DC were differentiated in vitro for 7 days with granulocyte macrophage colony stimulating factor and IL-4 in the presence or absence of dexamethasone 10(-8) M (Dex). Dex-treated DC showed an enhancement of mannose receptor (MR)-mediated endocytosis (measured as uptake of FITC-dextran) and of fluid-phase endocytosis [measured as uptake of Lucifer yellow (LY)] The effect was dose dependent and correlated with the length of exposure to Dex. The expression of receptors involved in antigen capture was investigated by FACS analysis. Dex up-regulates MR, CD16 and CD32 expression on DC. After maturation with tumor necrosis factor-alpha or CD40 ligand in Dex-treated DC, despite a reduction induced by maturation the endocytic activity of FITC-dextran and LY, the expression of MR, CD16 and CD32 remained higher than in control DC. In view of the fact that antigen capture was increased in cells cultured with Dex, we evaluated the ability to present soluble antigen that needs to be taken up and processed. Cells differentiated in the presence of Dex showed much lower efficiency in presenting tetanus toxin to specific autologous T cell lines. In conclusion our data suggest a new mechanism by which GC may influence immune responses. In fact with the increase in endocytic activity, Dex favors the scavenging of antigen from the external milieu, decreasing antigen concentration and availability, and simultaneously inhibiting the capacity to stimulate T cells.
Piemonti
L
L
Laboratory of Experimental Surgery, Surgical Department, S. Raffaele Scientific Institute, 20132 Milan, Italy.
Monti
P
P
Allavena
P
P
Leone
B E
BE
Caputo
A
A
Di Carlo
V
V
D017951:Antigen Presentation / Q000187:drug effects; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D003911:Dextrans / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004705:Endocytosis; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D005938:Glucocorticoids / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology
D003911:Dextrans; D005938:Glucocorticoids; C015219:fluorescein isothiocyanate dextran; D015847:Interleukin-4; D003907:Dexamethasone; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D016650:Fluorescein-5-isothiocyanate