Xiao Bao-Guo, Liu Xuan, Link Hans
Division of Neuroimmunology, Neurotec Department, Karolinska Institute, Alfred Nobels Allé 10, 141 83 Stockholm, Sweden.
Steroids. 2004 Sep;69(10):653-9. doi: 10.1016/j.steroids.2004.05.019.
Estrogen results in the suppression of experimental allergic encephalomyelitis (EAE), a frequently used experimental animal model of multiple sclerosis (MS). The mechanism by which estrogen acts in diseases with an autoimmune background is less clear. Here, we used splenic dendritic cells (DC) from the Lewis rats EAE model as target cells, and explored the pathway of estrogen in immune modulation. Estrogen did not affect the expression of MHC class II, CD80 and CD86 by DC, but inhibited the ability of DC to stimulate T cell proliferation and production of both Th1 and Th2 cytokines. This was accompanied by increased T cell apoptosis. Estrogen up-regulated DC to express indoleamine 2,3-dioxygenase (IDO) which can limit T cell responses. The effects of estrogen-exposed DC on T cell proliferation and apoptosis were partly abolished by addition of an IDO inhibitor (1-methyl-dl-tryptophan, 1-MT), indicating that estrogen-exposed DC induced IDO-dependent T cell suppression. Our data support the hypothesis that the estrogen-induced suppression of EAE, as well as the reduction in number of MS relapses observed during pregnancy, may be related to the estrogen-DC-IDO axis. This observation could open up a novel therapeutic target for influencing the course of MS and other diseases with an autoimmune diseases background.
雌激素可抑制实验性自身免疫性脑脊髓炎（EAE），这是一种常用于多发性硬化症（MS）研究的实验性动物模型。雌激素在自身免疫性疾病中的作用机制尚不清楚。在此，我们以Lewis大鼠EAE模型的脾树突状细胞（DC）作为靶细胞，探讨雌激素在免疫调节中的作用途径。雌激素不影响DC表面MHC II类分子、CD80和CD86的表达，但抑制DC刺激T细胞增殖以及Th1和Th2细胞因子产生的能力。这伴随着T细胞凋亡增加。雌激素上调DC表达吲哚胺2,3-双加氧酶（IDO），而IDO可限制T细胞反应。添加IDO抑制剂（1-甲基-dl-色氨酸，1-MT）可部分消除雌激素处理的DC对T细胞增殖和凋亡的影响，表明雌激素处理的DC诱导了IDO依赖的T细胞抑制。我们的数据支持以下假说：雌激素诱导的EAE抑制以及孕期MS复发次数减少可能与雌激素-DC-IDO轴有关。这一发现可能为影响MS病程以及其他自身免疫性疾病开辟新的治疗靶点。
