Modulation of macrophage differentiation and activation by decoy receptor 3.

Decoy receptor 3 (DcR3) is a soluble receptor of the tumor necrosis factor receptor su- perfamily and is readily detected in certain can- cer patients. Recently, we demonstrated that DcR3.Fc-treated dendritic cells skew T cell re- sponses to a T helper cell type 2 phenotype. In this study, we further asked its ability to modulate CD14 monocyte differentiation into macro- phages induced by macrophage-colony stimulating factor in vitro. We found that DcR3.Fc was able to modulate the expression of several macrophage markers, including CD14, CD16, CD64, and hu- man leukocyte antigen-DR. In contrast, the ex- pression of CD11c, CD36, CD68, and CD206 (mannose receptor) was not affected in the in vitro culture system. Moreover, phagocytic activity to- ward immune complexes and apoptotic bodies as well as the production of free radicals and proin- flammatory cytokines in response to lipopolysac- charide were impaired in DcR3.Fc-treated mono- cyte-derived macrophages. This suggests that DcR3.Fc might have potent, suppressive effects to down-regulate the host-immune system. J. Leukoc. Biol. 75: 486-494; 2004.