Prenatal Medicine, Department of Biomedicine, University and University Hospital Basel, Basel, Switzerland.
Systems Biology of Reproduction Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary.
Front Immunol. 2020 Feb 12;11:145. doi: 10.3389/fimmu.2020.00145. eCollection 2020.
Termed as galectin-13, placental protein 13 (PP13) is exclusively expressed in the placenta of anthropoid primates. Research on PP13 in normal and pathologic pregnancies show alteration of PP13 concentrations in pregnancy affected by preeclampsia or gestational diabetes. Galectins are also described as potent immunomodulators, and PP13 regulates T cell function in the placenta. Therefore, this study aims to investigate the effects of PP13 on neutrophils; a cell type often ignored in pregnancy, but present in the uterus and placenta from the early stages of pregnancy. Since neutrophil function is dysregulated during pathologic pregnancies, a link between PP13 and neutrophil activity is possible. We determined that PP13 reduces the apoptosis rate in neutrophils. Also, PP13 increases the expression of PD-L1 and production of HGF, TNF-α, reactive oxygen species (ROS), and MMP-9 in these cells. This phenotype resembles one observed in permissive tumor neutrophils; able to sustain tissue and vessel growth, and inhibit T cell activation. At the same time, PP13 does not alter all neutrophil functions, i.e., extrusion of neutrophil extracellular traps, degranulation, phagocytosis, and ROS production following bacterial exposure. PP13 seems to play an essential role in regulating the activity of neutrophils in the placenta by polarizing them toward a placental-growth-permissive phenotype.
被称为半乳糖凝集素-13(galectin-13)的胎盘蛋白 13(PP13)仅在类人灵长类动物的胎盘组织中表达。研究表明,在受子痫前期或妊娠期糖尿病影响的妊娠中,PP13 的浓度会发生变化。半乳糖凝集素也被描述为有效的免疫调节剂,PP13 调节胎盘 T 细胞的功能。因此,本研究旨在研究 PP13 对中性粒细胞的影响;中性粒细胞是一种在妊娠中经常被忽视的细胞类型,但在妊娠早期的子宫和胎盘中存在。由于中性粒细胞在病理性妊娠中功能失调,因此 PP13 与中性粒细胞活性之间可能存在联系。我们发现 PP13 可降低中性粒细胞的凋亡率。此外,PP13 增加了 PD-L1 的表达以及 HGF、TNF-α、活性氧(ROS)和 MMP-9 的产生。这种表型类似于在允许肿瘤发生的中性粒细胞中观察到的表型;能够维持组织和血管的生长,并抑制 T 细胞的激活。同时,PP13 不会改变中性粒细胞的所有功能,例如,在暴露于细菌后,中性粒细胞的细胞外陷阱的挤出、脱粒、吞噬和 ROS 的产生。PP13 似乎通过将中性粒细胞向有利于胎盘生长的表型极化,在调节胎盘中性粒细胞活性方面发挥了重要作用。