Key Laboratory of Pathogen Biology of Jiangsu Province, Department of Pathogen Biology, Nanjing Medical University, Nanjing, China.
Xuanwumen Community Health Service Center of Xuanwu District, Nanjing, China.
Front Immunol. 2018 May 18;9:1102. doi: 10.3389/fimmu.2018.01102. eCollection 2018.
Estradiol (E2) plays a crucial and intricate role during pregnancy to mediate several aspects of the pregnancy process. A perplexing phenomenon in congenital toxoplasmosis is that the severity of ()-mediated adverse pregnancy outcome is closely related with time of primary maternal infection during pregnancy. In this study, the results showed that infection in early pregnancy was more likely to induce miscarriage in mice than in late pregnancy, which may be related to inflammation of the maternal-fetal interface. Meanwhile, the infection-induced-apoptotic rate of Tregs was higher and the expression of programmed death-1 (PD-1) on Tregs was lower in early pregnancy than in late pregnancy. As the level of E2 in mouse serum gradually increased with the development of pregnancy, we proposed that E2 may contribute to the discrepancy of Tregs at different stages of pregnancy. Thus, we investigated and effects of E2 in regulating Tregs. We found that E2 could protect Tregs against apoptosis and upregulate the expression of PD-1 on Tregs in a dose-dependent manner through ERα. Likewise, the simulated mid-pregnancy level of E2 in nonpregnant mice also alleviated the infection-induced apoptosis of Tregs and potentiated the PD-1 expression on Tregs. Therefore, in the pathogenesis of -induced abnormal pregnancy, E2 helped maintain the immune balance and improve the pregnancy outcome through regulating Tregs. This finding illustrates the intricate working of hormone-immune system interaction in infection-induced abnormal pregnancy.
雌二醇（E2）在妊娠期间发挥着至关重要且复杂的作用，调节妊娠过程的多个方面。先天性弓形虫病的一个令人费解的现象是，母体感染初次发生在妊娠早期时，更易导致不良妊娠结局，这与妊娠期间初次感染的时间密切相关。在本研究中，结果表明，妊娠早期感染更可能导致小鼠流产，而不是妊娠晚期感染，这可能与母体-胎儿界面的炎症有关。同时，妊娠早期感染诱导的 Tregs 凋亡率高于妊娠晚期，且 Tregs 上程序性死亡受体 1（PD-1）的表达也较低。由于妊娠期间小鼠血清中 E2 水平随着妊娠的发展逐渐升高，我们推测 E2 可能导致妊娠不同阶段 Tregs 出现差异。因此，我们研究了 E2 对 Tregs 的调节作用。我们发现，E2 通过 ERα 以剂量依赖的方式保护 Tregs 免受凋亡，并上调 Tregs 上 PD-1 的表达。同样，在非妊娠小鼠中模拟妊娠中期的 E2 水平也能减轻 感染诱导的 Tregs 凋亡，并增强 Tregs 上 PD-1 的表达。因此，在弓形虫感染导致的异常妊娠发病机制中，E2 通过调节 Tregs 帮助维持免疫平衡并改善妊娠结局。这一发现说明了激素-免疫系统相互作用在感染引起的异常妊娠中的复杂性。
