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Sildenafil might impair maternal-fetal immunotolerance by suppressing myeloid-derived suppressor cells in mice.
Journal of Reproductive Immunology ( IF 2.9 ) Pub Date : 2020-07-03 , DOI: 10.1016/j.jri.2020.103175
H H Jiang 1 , K X Wang 1 , K H Bi 2 , Z M Lu 2 , J Q Zhang 2 , H R Cheng 2 , M Y Zhang 2 , J J Su 2 , Y X Cao 1
Affiliation  

Myeloid-derived suppressor cells (MDSCs) as an important population of immune cells were found to restrain T cell function, polarize T-helper cells (Th) 1/Th2 toward Th2 response and induce regulatory T cells (Tregs), therefore enhancing the immunotolerance during pregnancy. Sildenafil has been applied for poor endometrial quality in implantation failure patients. Nevertheless, investigations have shown that sildenafil could reduce MDSCs-dependent immunosuppression. Whether sildenafil affects embryo implantation by suppressing MDSCs? To address this question, using the mice model, we investigated the amounts of immune cells in peripheral blood and endometrial cells from control group (CG), sildenafil low-dose group (LDG) and high-dose group (HDG). We found that both treatment groups displayed a marked deficiency in polymorphonuclear (PMN)-MDSCs and Th2 from mice blood and endometrium as compared to these from CG. The frequency of Tregs in endometrium from HDG was lower than those from CG. Th1/Th2 ratio in both periphery and uterus from study groups showed a significant increase as compared to those from CG. By relevance analysis, we found that the level of Tregs positively correlated with the level of PMN-MDSCs, whereas the Th1/Th2 ratio negatively correlated with the frequency of PMN-MDSCs in uterus. Moreover, there was a positive relationship between the amount of blood PMN-MDSCs and endometrial PMN-MDSCs. These results suggest that we should carefully weigh the pros and cons of using sildenafil when applied to patients with poor endometrial receptivity.



中文翻译:

西地那非可能通过抑制小鼠骨髓源性抑制细胞来损害母胎免疫耐受。

髓源性抑制细胞 (MDSCs) 作为重要的免疫细胞群被发现抑制 T 细胞功能,将 T 辅助细胞 (Th) 1/Th2 极化为 Th2 反应并诱导调节性 T 细胞 (Tregs),从而增强免疫耐受性怀孕期间。西地那非已用于治疗植入失败患者的子宫内膜质量差。尽管如此,研究表明西地那非可以减少 MDSCs 依赖性免疫抑制。西地那非是否通过抑制 MDSCs 影响胚胎植入?为了解决这个问题,我们使用小鼠模型研究了对照组(CG)、西地那非低剂量组(LDG)和高剂量组(HDG)的外周血和子宫内膜细胞中免疫细胞的数量。我们发现,与来自 CG 的这些相比,两个治疗组都显示出小鼠血液和子宫内膜中的多形核 (PMN)-MDSC 和 Th2 明显缺乏。HDG 子宫内膜中 Tregs 的频率低于 CG。与 CG 组相比,研究组外周和子宫的 Th1/Th2 比值均显着增加。通过相关性分析,我们发现Tregs的水平与PMN-MDSCs的水平呈正相关,而Th1/Th2比值与子宫内PMN-MDSCs的频率呈负相关。此外,血液中 PMN-MDSCs 的数量与子宫内膜 PMN-MDSCs 之间存在正相关关系。这些结果表明,当应用于子宫内膜容受性差的患者时,我们应该仔细权衡使用西地那非的利弊。

更新日期:2020-07-24
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