Continuous activation of polymorphonuclear myeloid-derived suppressor cells during pregnancy is critical for fetal development
Continuous activation of polymorphonuclear myeloid-derived suppressor cells during pregnancy is critical for fetal development
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DOI：
10.1038/s41423-021-00704-w
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发表时间：
2021-06-07
影响因子：
24.1
通讯作者：
He, Yumei
中科院分区：
文献类型：
--
作者：
Shi, Mengyu;Chen, Ziyang;He, Yumei
母体免疫系统在维持对半同种异体胎儿的免疫耐受性以成功妊娠方面至关重要。虽然研究表明，骨髓来源的抑制细胞（MDSC）在维持胎儿-母体耐受中发挥重要作用，但对MDSC在宫内生长迟缓（IUGR）妊娠中的作用知之甚少。在这里，我们报道了多形核细胞骨髓源性抑制细胞（PMN-MDSC）在妊娠期间的激活与胎儿生长密切相关。在人类中，E类清道夫受体1（SR-E1），人类PMN-MDSC的独特标志物，用于研究妊娠期间PMN-MDSC的功能。在妊娠的所有阶段都观察到SR-E1（+）PMN-MDSC的持续活化，伴随着高细胞水平的ROS和STAT 6信号转导介导的β-淀粉酶-1活性。IUGR组SR-E1（+）PMN-MDSCs的抑制活性、增殖酶-1活性、ROS水平、STAT 6磷酸化水平均低于正常组，同时伴有炎症因子水平的升高。此外，SR-E1（+）PMN-MDSC的数量与IUGR妊娠新生儿的不良结局呈负相关。在小鼠中，与正常妊娠相比，在IUGR妊娠中也观察到细胞群、抑制活性、靶向表达水平和STAT 6磷酸化水平的降低，这些正常妊娠通过过继转移来自妊娠小鼠的PMN-MDSC来挽救。有趣的是，人和小鼠胎盘PMN-MDSC分泌的生长促进因子（GPFs）在胎儿发育中起着至关重要的作用。这些发现共同支持PMN-MDSCs在妊娠中具有另一种新的作用，可以改善不良的新生儿结局。
The maternal immune system is vital in maintaining immunotolerance to the semiallogeneic fetus for a successful pregnancy. Although studies have shown that myeloid-derived suppressor cells (MDSCs) play an important role in maintaining feto-maternal tolerance, little is known about the role of MDSCs in pregnancies with intrauterine growth retardation (IUGR). Here, we reported that the activation of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) during pregnancy was closely associated with fetal growth. In humans, class E scavenger receptor 1 (SR-E1), a distinct marker for human PMN-MDSCs, was used to investigate PMN-MDSC function during pregnancy. Continuous activation of SR-E1(+) PMN-MDSCs was observed in all stages of pregnancy, accompanied by high cellular levels of ROS and arginase-1 activity, mediated through STAT6 signaling. However, SR-E1(+) PMN-MDSCs in pregnancies with IUGR showed significantly lower suppressive activity, lower arginase-1 activity and ROS levels, and decreased STAT6 phosphorylation level, which were accompanied by an increase in inflammatory factors, compared with those in normal pregnancies. Moreover, the population of SR-E1(+) PMN-MDSCs was negatively correlated with the adverse outcomes of newborns from pregnancies with IUGR. In mice, decreases in cell population, suppressive activity, target expression levels, and STAT6 phosphorylation levels were also observed in the pregnancies with IUGR compared with the normal pregnancies, which were rescued by the adoptive transfer of PMN-MDSCs from pregnant mice. Interestingly, the growth-promoting factors (GPFs) secreted by placental PMN-MDSCs in both humans and mice play a vital role in fetal development. These findings collectively support that PMN-MDSCs have another new role in pregnancy, which can improve adverse neonatal outcomes.