Zhu W H, Lu C Z, Huang Y M, Link H, Xiao B G
Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Mult Scler. 2007 Jan;13(1):33-40. doi: 10.1177/1352458506071171.
The basis for the reduced relapse rate of multiple sclerosis (MS) during pregnancy remains unexplained but, if defined, could create novel treatment options. Estrogen constitutes one candidate molecule, but the mechanism by which estrogen may affect MS during pregnancy is unclear. In this study, we used monocyte-derived dendritic cells (DCs) from MS patients to explore the estrogen (17-beta-estradiol)-related pathway of immune modulation. Estrogen induced the expression of indoleamine 2,3-dioxygenase (IDO) on DCs, limiting T-cell proliferation and both Th1 and Th2 cytokine production. The suppression of T-cell proliferation mediated by estrogen-exposed DCs was partly abolished by the IDO-inhibitor, 1-methyl-dl-tryptophan, indicating that estrogen-exposed DCs induced IDO-dependent T-cell suppression. Our data support the hypothesis that the change in the clinical course of MS observed in pregnancy may be related to the estrogen-DC-IDO axis, which could represent a novel target for MS therapy.
孕期多发性硬化症（MS）复发率降低的原因尚不清楚，但一旦明确，可能会产生新的治疗方案。雌激素是一个候选分子，但雌激素在孕期影响MS的机制尚不清楚。在本研究中，我们使用来自MS患者的单核细胞衍生树突状细胞（DC）来探索雌激素（17-β-雌二醇）相关的免疫调节途径。雌激素诱导DC上吲哚胺2,3-双加氧酶（IDO）的表达，限制T细胞增殖以及Th1和Th2细胞因子的产生。IDO抑制剂1-甲基-dl-色氨酸部分消除了雌激素处理的DC介导的T细胞增殖抑制，表明雌激素处理的DC诱导了IDO依赖性T细胞抑制。我们的数据支持这样的假设，即孕期观察到的MS临床病程变化可能与雌激素-DC-IDO轴有关，这可能代表MS治疗的一个新靶点。
