Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Hum Immunol. 2022 Aug-Sep;83(8-9):628-636. doi: 10.1016/j.humimm.2022.07.004. Epub 2022 Jul 26.
Preeclampsia (PE) is a severe complication in pregnancy, and its symptoms (proteinuria and hypertension) manifest after 20 weeks of gestation, affecting up to 8 % of pregnancies. The pregnant women's immune system uses different tolerance mechanisms to deal with a semi-allogeneic fetus. The T-cell subsets including CD8+, CD4+, and Treg play a critical role in maintaining pregnancies. The expression of immune checkpoint molecules in T-cells can ensure pregnancy at the feto-maternal interface by controlling immune responses. This research aims to evaluate the expression level of immune checkpoint factors, including PD-1, LAG-3, CTLA-4, and TIM-3 in normal pregnant women and PE patients. Decidual tissue was collected from 50 participants (25 PE and 25 control). For evaluating the genes expression, real-time PCR was employed. The western blot was used to assess the proteins level. The results of real-time PCR indicated significantly decreased expression level of these immune checkpoints in PE patients. In parallel to gene expression results, the protein level of PD-1, LAG-3, CTLA-4, and TIM-3 in the PE group was also reduced. We revealed that the profile of proteins and genes expression of immune checkpoints in the decidua of PE mothers are different from normal pregnancy and these results indicate aberrant expression of immune checkpoints such as PD-1, LAG-3, CTLA-4, and TIM-3 may cause maladaptation immune response which results in PE manifestation.
子痫前期(PE)是妊娠的严重并发症,其症状(蛋白尿和高血压)在妊娠 20 周后出现,影响高达 8%的妊娠。孕妇的免疫系统使用不同的耐受机制来应对半同种异体胎儿。T 细胞亚群包括 CD8+、CD4+和 Treg 在维持妊娠中起关键作用。T 细胞中免疫检查点分子的表达可以通过控制免疫反应来确保在胎-母界面的妊娠。本研究旨在评估免疫检查点因子 PD-1、LAG-3、CTLA-4 和 TIM-3 在正常孕妇和 PE 患者中的表达水平。从 50 名参与者(25 名 PE 和 25 名对照)中收集蜕膜组织。采用实时 PCR 评估基因表达。采用 Western blot 评估蛋白水平。实时 PCR 结果表明,PE 患者这些免疫检查点的表达水平显著降低。与基因表达结果平行,PE 组 PD-1、LAG-3、CTLA-4 和 TIM-3 的蛋白水平也降低。我们揭示了 PE 母亲蜕膜中免疫检查点的蛋白和基因表达谱与正常妊娠不同,这些结果表明 PD-1、LAG-3、CTLA-4 和 TIM-3 等免疫检查点的异常表达可能导致适应性免疫反应失调,从而导致 PE 表现。