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Blood, Vol. 95 No. 9 (May 1), 2000:
pp. 2875-2882
Nonsteroidal anti-estrogens inhibit the functional
differentiation of human monocyte-derived dendritic cells
Janne Komi and
Olli Lassila
From the Turku Immunology Centre, Department of Medical
Microbiology, Turku University, Kiinamyllynkatu 13, 20520 Turku,
Finland.
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.
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