Paharkova-Vatchkova Vladislava, Maldonado Ruben, Kovats Susan
Division of Immunology, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.
J Immunol. 2004 Feb 1;172(3):1426-36. doi: 10.4049/jimmunol.172.3.1426.
Sex biases in autoimmunity and infection suggest that steroid sex hormones directly modulate immune cells. We show in this study that 17-beta-estradiol (E2) promotes the differentiation of functional dendritic cells (DC) from murine bone marrow precursor cells. Remarkably, ex vivo DC differentiation was inhibited in steroid hormone-deficient medium, and was restored by addition of physiological amounts of E2, but not dihydrotestosterone. DC differentiation was inhibited by the estrogen receptor (ER) antagonists ICI 182,780 and tamoxifen, and from ERalpha(-/-) bone marrow cells, indicating that E2 acted via ERs. E2 addition was most effective in promoting DC differentiation immediately ex vivo, but did not increase DC proliferation. E2 treatment specifically promoted differentiation of a CD11c(+) CD11b(int) DC population that displayed high levels of cell surface MHC class II and CD86, suggesting that E2 could augment numbers of potent APC. DC that differentiated in E2-supplemented medium were fully functional in their capability to mediate presentation of self and foreign Ags and stimulate the proliferation of naive CD4(+) T cells. The requirement for estrogen during DC differentiation suggests a mechanism by which E2 levels in peripheral tissues might modulate both the number and functional capabilities of DC in vivo, thereby influencing immune responses.
自身免疫和感染中的性别偏见表明，类固醇性激素直接调节免疫细胞。我们在本研究中表明，17-β-雌二醇（E2）可促进功能性树突状细胞（DC）从小鼠骨髓前体细胞分化而来。值得注意的是，在缺乏类固醇激素的培养基中，体外DC分化受到抑制，添加生理量的E2可恢复分化，但二氢睾酮则无此作用。雌激素受体（ER）拮抗剂ICI 182,780和他莫昔芬以及ERα（-/-）骨髓细胞均可抑制DC分化，表明E2通过ER发挥作用。添加E2在体外立即促进DC分化方面最为有效，但不会增加DC增殖。E2处理特异性促进了CD11c（+）CD11b（int）DC群体的分化，该群体显示出高水平的细胞表面MHC II类分子和CD86，这表明E2可以增加强效抗原呈递细胞的数量。在补充E2的培养基中分化的DC在介导自身和外来抗原呈递以及刺激初始CD4（+）T细胞增殖的能力方面具有完全功能。DC分化过程中对雌激素的需求提示了一种机制，通过该机制外周组织中的E2水平可能在体内调节DC的数量和功能能力，从而影响免疫反应。
