Pregnancy level of estrogen attenuates experimental autoimmune encephalomyelitis in both ovariectomized and pregnant C57BL/6 mice through expansion of Treg and Th2 cells
Pregnancy level of estrogen attenuates experimental autoimmune encephalomyelitis in both ovariectomized and pregnant C57BL/6 mice through expansion of Treg and Th2 cells
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DOI：
10.1016/j.jneuroim.2014.10.004
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发表时间：
2014-12-15
影响因子：
3.3
通讯作者：
Mahmoudi, Mahmoud
中科院分区：
文献类型：
--
作者：
Haghmorad, Dariush;Amini, Abbas Ali;Mahmoudi, Mahmoud
高水平的雌激素和雌三醇等性类固醇可能对自身免疫性疾病（包括多发性硬化症和类风湿性关节炎）的妊娠抑制作用产生影响。本研究旨在揭示雌激素缓解多发性硬化症的分子和细胞机制。用MOG(35-55)免疫雌性C57BL/6小鼠。每天监测临床评分和其他相关参数。进行脑和脊髓组织学检查以测量淋巴细胞浸润和中枢神经系统脱髓鞘。通过 ELISA、流式细胞术和实时 PCR 测定 Th1/Th2/Th17 和 Treg 细胞谱。通过实时 PCR 评估 CNS 中的转录因子表达水平，并通过流式细胞术检查探索 T 细胞分化。妊娠和妊娠水平的雌激素可减轻EAE诱导小鼠的临床表现，减少中枢神经系统脱髓鞘和细胞浸润，抑制脾脏T细胞增殖，增强脾细胞抗炎细胞因子的产生，增加Th2和Treg细胞的百分比。此外，中枢神经系统Th1/Th2/Th17和Treg细胞转录因子和相关细胞因子的实时PCR结果显示，Th1和Th17转录因子（包括T-bet和ROR-gamma t）表达水平降低，Th1和Th17细胞因子（包括IFN-γ、TNF-α、IL-17和IL-23）表达水平降低。这些结果首次表明妊娠和妊娠水平的雌激素通过诱导 CNS 中 Foxp3 和 GATA3 的表达促进 Treg 和 Th2 分化，从而改善 EAE 状况。此外，妊娠和妊娠期间雌激素水平降低了中枢神经系统中 T-bet 和 ROR-gamma t 的 mRNA 水平。 (C) 2014 Elsevier B.V. 保留所有权利。
Pregnancy suppressive effect on autoimmune diseases including Multiple Sclerosis and Rheumatoid Arthritis may result from high levels of sex steroids such as estrogen and estriol. This study was designed to reveal the molecular and cellular mechanisms underlying the effect of estrogen on MS alleviation. Female C57BL/6 mice were immunized with MOG(35-55). Clinical scores and other relevant parameters were monitored daily. Brain and spinal cord histology was performed to measure lymphocyte infiltration and central nervous system demyelination. Th1/Th2/Th17 and Treg cell profiles were determined through ELISA, flow cytometry, and real-time PCR. Transcription factor expression levels in the CNS were assessed by real-time PCR and T cell differentiation was explored through flow cytometry examination. Pregnancy and pregnancy level of estrogen alleviated clinical manifestations in EAE induced mice, reduced CNS demyelination and cell infiltration, suppressed spleen T cell proliferation, enhanced production of anti-inflammatory cytokines in splenocytes and increased the percentage of Th2 and Treg cells. Furthermore, the results of real-time PCR for transcription factors and related cytokines of Th1/Th2/Th17 and Treg cells in CNS showed reduced expression levels of Th1 and Th17 transcription factors, including T-bet and ROR-gamma t, and decreased Th1 and Th17 cytokines including IFN-gamma, TNF-alpha, IL-17 and IL-23. These results are the first to indicate that pregnancy and pregnancy level of estrogen ameliorate the EAE condition by favoring Treg and Th2 differentiation through induced expression of Foxp3 and GATA3 in the CNS. Moreover, pregnancy and pregnancy level of estrogen decreased mRNA levels of T-bet and ROR-gamma t in the CNS. (C) 2014 Elsevier B.V. All rights reserved.