Wang Hong, Lu Wenting, Zhu Mengru, Yu Yongli, Wang Liying
Department of Molecular Biology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, P.R. China.
Department of Obstetrics and gynecology, The First Hospital of Jilin University, Jilin University, Changchun, Jilin, P.R. China.
Cell Mol Life Sci. 2025 Aug 29;82(1):324. doi: 10.1007/s00018-025-05858-8.
TLR9 is an intracellular receptor that can also be localized to the cell surface, called sTLR9. sTLR9 is thought to have a negative immunomodulatory effect, which is conductive to the maintenance of immune tolerance. Since pregnancy is a physiological process accompanied with inflammation experienced by pregnant women while maintaining immune tolerance to the fetus, the change in sTLR9 of immune cells during pregnancy are worth studying. In this study, we first found that with the progress of pregnancy, the most significant change in PWBCs of pregnant women was the increasing percentage of neutrophils (Neu%) accompanied by the decreasing sTLR9 Neu%. Then, we found that percentages and sTLR9 levels of sTLR9 Neu were significantly higher in pregnant mice than those in non-pregnant mice, while the latter was obviously elevated in the first and second trimesters than that in third trimester and after delivery. In mice, the TLR9 agonist CpG ODN induced a proinflammatory environment characterized by a significant increase in Neu% and a decrease or no change in sTLR9 Neu%. In this case, the delivery time of pregnant mice was not affected, but their newborn mice showed significant weight loss. These results link sTLR9 as an immune cell phenotype to immune tolerance status during pregnancy, providing a kind of new insights into the mechanisms by which pregnant mother maintain immune tolerance to the fetus.
Toll样受体9（TLR9）是一种细胞内受体，也可定位于细胞表面，称为可溶性TLR9（sTLR9）。sTLR9被认为具有负性免疫调节作用，有助于维持免疫耐受。由于妊娠是一个伴随着孕妇炎症反应同时又要维持对胎儿免疫耐受的生理过程，孕期免疫细胞中sTLR9的变化值得研究。在本研究中，我们首先发现随着妊娠进展，孕妇外周血白细胞（PWBCs）中最显著的变化是中性粒细胞百分比（Neu%）增加，同时sTLR9 Neu%降低。然后，我们发现妊娠小鼠中sTLR9 Neu的百分比和sTLR9水平显著高于未妊娠小鼠，而后者在妊娠前三个月明显高于妊娠晚期和分娩后。在小鼠中，TLR9激动剂CpG ODN诱导了一种促炎环境，其特征是Neu%显著增加，sTLR9 Neu降低或无变化。在这种情况下，妊娠小鼠的分娩时间未受影响，但它们的新生小鼠体重显著减轻。这些结果将sTLR9作为一种免疫细胞表型与妊娠期间的免疫耐受状态联系起来，为妊娠母亲维持对胎儿免疫耐受的机制提供了一种新的见解。
