Nonsteroidal anti-estrogens inhibit the functional differentiation of human monocyte-derived dendritic cells

Dendritic cells (DC) are professional antigen-presenting cells with a uniqu e capacity to initiate and regulate immune responses. Immature CD1a(+) DC c an be cultured from CD14(+) monocytes in the presence of interleukin (IL)-4 and granulocyte macrophage colony-stimulating factor in vitro. Results of this study show that the nonsteroidal anti-estrogens toremifene and tamoxif en inhibit this differentiation. In the presence of anti-estrogens the cell s lose CD14 expression, but remain CD1a(-) and clearly have less dendritic processes than immature DC, Functionally, anti-estrogen-treated cells are i nferior to immature DC in inducing proliferation of allogeneic T cells and in producing IL-12 p70 protein after CD40 ligation, The expression of the c ostimulatory molecules CD80 and CD86 is differentially regulated by anti-es trogens during DC differentiation. Furthermore, antiestrogens are also able to inhibit the terminal maturation of DC. By inhibiting the functional dif ferentiation of DC, antiestrogens may have a role in the treatment and prev ention of autoimmune diseases. (Blood. 2000;95:2875-2882) (C) 2000 by The A merican Society of Hematology.