17-Oestradiol enhances the expansion and activation of myeloid-derived suppressor cells via signal transducer and activator of transcription (STAT)-3 signalling in human pregnancy
17-Oestradiol enhances the expansion and activation of myeloid-derived suppressor cells via signal transducer and activator of transcription (STAT)-3 signalling in human pregnancy
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17-雌二醇通过信号转导器和转录激活剂 (STAT)-3 信号传导增强人类妊娠中骨髓源性抑制细胞的扩增和激活
DOI：
10.1111/cei.12790
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发表时间：
2016-07-01
影响因子：
4.6
通讯作者：
Zhou, J.
中科院分区：
文献类型：
--
作者：
Pan, T.;Zhong, L.;Zhou, J.
在成功妊娠期间，母体免疫系统在维持对半同种异体胎儿抗原的免疫耐受性方面起着关键作用。最近的研究表明，髓源性抑制细胞（MDSC）是建立胎儿-母体耐受的积极参与者;然而，其潜在机制仍然知之甚少。在这项研究中，我们观察到孕妇外周血中单核细胞MDSC（M-MDSC）的显著扩增，其以活性氧依赖性方式抑制T细胞反应，并需要细胞-细胞接触。M-MDSC数量与血清雌、孕激素水平呈正相关。给予17-雌二醇，而不是孕酮，通过信号转导和转录激活因子（STAT）-3增强M-MDSC的扩增和抑制活性。用STAT-3抑制剂JSI-124预处理几乎完全消除了17-雌二醇对MDSC的作用。总的来说，这些结果表明，17-雌二醇诱导的STAT-3信号转导在人类妊娠期间MDSC的扩增和激活中起着重要作用，这可能有利于开发预防免疫相关流产的新治疗策略。
During a successful pregnancy, the maternal immune system plays a critical role in maintaining immunotolerance towards semi-allogeneic fetal antigens. Recent studies have indicated that myeloid-derived suppressor cells (MDSCs) are active players in establishing fetal-maternal tolerance; however, the underlying mechanism remains poorly understood. In this study, we observed a significant expansion of monocytic MDSCs (M-MDSCs) in the peripheral blood of pregnant women, which suppressed T cell responses in a reactive oxygen species-dependent manner and required cell-cell contact. The number of M-MDSCs correlated positively with serum oestrogen and progesterone levels. Administration of 17-oestradiol, but not progesterone, enhanced both the expansion and suppressive activity of M-MDSCs through signal transducer and activator of transcription (STAT)-3. Pretreatment with STAT-3 inhibitor JSI-124 almost completely abrogated the effects of 17-oestradiol on MDSCs. Collectively, these results demonstrate that 17-oestradiol-induced STAT-3 signalling plays an important role in both the expansion and activation of MDSCs during human pregnancy, which may benefit the development of novel therapeutic strategies for prevention of immune-related miscarriage.