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

Nonsteroidal anti-estrogens inhibit the functional differentiation of human monocyte-derived dendritic cells
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DOI:
10.1182/blood.v95.9.2875.009k12_2875_2882
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发表时间:
2000-05-01
期刊:
影响因子:
20.3
通讯作者:
Lassila, O
Lassila, O
中科院分区:
医学1区
文献类型:
--
作者:
Komi, J;Lassila, O

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树突状细胞(DC)是专职的抗原呈递细胞,具有启动和调节免疫反应的独特能力。在IL-4和粒细胞-巨噬细胞集落刺激因子的作用下,可以从CD 14(+)单核细胞中体外培养出未成熟的CD 1a(+)DC。这项研究的结果表明,非甾体抗雌激素托瑞米芬和他莫昔芬抑制这种分化。在抗雌激素存在下,细胞失去CD 14表达,但保持CD 1a(-),并且明显具有比未成熟DC少的树突状突起。在功能上,抗雌激素处理的细胞在诱导同种异体T细胞增殖和在CD 40连接后产生IL-12 p70蛋白方面劣于未成熟DC,共刺激分子CD 80和CD 86的表达在DC分化过程中受到抗雌激素的差异调节。此外,抗雌激素也能够抑制DC的终末成熟。通过抑制DC的功能分化,抗雌激素可能在治疗和预防自身免疫性疾病中发挥作用。(血。2000;95:2875-2882)(C)2000由美国血液学学会。
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, antiestrogens are also able to inhibit the terminal maturation of DC. By inhibiting the functional differentiation of DC, antiestrogens may have a role in the treatment and prevention of autoimmune diseases. (Blood. 2000;95:2875-2882) (C) 2000 by The American Society of Hematology.