INTERLEUKIN-10 INCREASES MANNOSE RECEPTOR EXPRESSION AND ENDOCYTIC ACTIVITY IN MONOCYTE-DERIVED DENDRITIC CELLS

Human monocyte-derived dendritic cells were differentiated in vitro fo r 7 days with granulocyte macrophage-colony stimulating factor and int erleukin-13. These cultured dendritic cells are at an immature stage o f differentiation and exhert high endocytic activity via surface manno se receptor and via fluid-phase macropinocytosis. We have investigated the modulation of endocytosis by interleukin-10 in these cells. When added during the last 24 h of the 7-day culture, interleukin-10 signif icantly stimulated the uptake of fluorescein-labelled dextran (39 +/- 16% increase, mean +/-SD of 6 experiments), a sugar binding to the man nose receptor. This effect was dose dependent and correlated with the length of exposure to interleukin-10, with a maximal effect (more than seven-fold increase) when the cytokine was added at the beginning of the culture (day 0). The interleukin-10-increased fluorescein-labelled -dextran endocytosis was mostly mediated via the mannose receptor, as unlabelled mannose and specific antimannose receptor monoclonal antibo dy inhibited most of the uptake. Moreover, interleukin-10-treated cell s expressed increased levels (up to four-fold) of mannose receptor. In terleukin-10 also increased, although to a lesser extent, the fluid-ph ase endocytosis (macropinocytosis) of fluorescein-labelled albumin. In terleukin-10 had the opposite effect on the differentiation and functi onal activity of monocyte-derived dendritic cells; cells having a very low stimulatory capacity and reduced expression of MHC class II and C D1a after a 7-day exposure. Thus interleukin-10 had a strong immunosup pressive effect on the differentiation and functional activity of mono cyte-derived dendritic cells and yet strongly stimulated endocytosis i n these cells. We speculate that an increased endocytic activity would eventually result in a decreased availability of antigens in the exte rnal milieu, thus contributing to the immunosuppressive and tolerogeni c activity of interleukin-10.