Nonsteroidal anti-estrogens inhibit the functional differentiation of human monocyte-derived dendritic cells.
Dendritic cells (DC) are professional antigen-presenting cells with a unique capacity to initiate and regulate immune responses. Immature CD1a(+) DC can 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 tamoxifen inhibit this differentiation. In the presence of anti-estrogens the cells lose CD14 expression, but remain CD1a(-) and clearly have less dendritic processes than immature DC. Functionally, anti-estrogen-treated cells are inferior to immature DC in inducing proliferation of allogeneic T cells and in producing IL-12 p70 protein after CD40 ligation. The expression of the costimulatory molecules CD80 and CD86 is differentially regulated by anti-estrogens during DC differentiation. Furthermore, anti-estrogens are also able to inhibit the terminal maturation of DC. By inhibiting the functional differentiation of DC, anti-estrogens may have a role in the treatment and prevention of autoimmune diseases. (Blood. 2000;95:2875-2882)
Komi
J
J
Turku Immunology Centre, Department of Medical Microbiology, Turku University, Kiinamyllynkatu 13, 20520 Turku, Finland. janne.komi@utu.fi
Lassila
O
O
D015703:Antigens, CD / Q000032:analysis / Q000276:immunology; D018949:Antigens, CD1 / Q000032:analysis; D018122:B7-1 Antigen / Q000276:immunology; D051940:B7-2 Antigen; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D020847:Estrogen Receptor Modulators / Q000494:pharmacology; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D007959:Lymphocyte Culture Test, Mixed; D008562:Membrane Glycoproteins / Q000276:immunology; D009000:Monocytes / Q000166:cytology / Q000276:immunology*; D011960:Receptors, Estrogen / Q000235:genetics; D013629:Tamoxifen / Q000494:pharmacology*; D017312:Toremifene / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
D015703:Antigens, CD; D018949:Antigens, CD1; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D020847:Estrogen Receptor Modulators; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D011960:Receptors, Estrogen; D016212:Transforming Growth Factor beta; D013629:Tamoxifen; D015847:Interleukin-4; D017312:Toremifene; D016178:Granulocyte-Macrophage Colony-Stimulating Factor