关键词: CD226 CD8 LAG-3 NK cells TIGIT early-onset preeclampsia immune checkpoint pathways

Mesh : Humans Female Pregnancy Pre-Eclampsia / immunology blood Killer Cells, Natural / immunology metabolism CD8-Positive T-Lymphocytes / immunology metabolism Adult Antigens, Differentiation, T-Lymphocyte / metabolism Immune Checkpoint Proteins / metabolism Case-Control Studies

来  源:   DOI:10.3390/ijms25158378   PDF(Pubmed)

Abstract:
Despite the numerous studies on the clinical aspects of early-onset preeclampsia, our understanding of the immunological consequences of inadequate placenta development remains incomplete. The Th1-predominance characteristic of early-onset preeclampsia significantly impacts maternal immunotolerance, and the role of immune checkpoint molecules in these mechanisms is yet to be fully elucidated. Our study aims to fill these crucial knowledge gaps. A total of 34 pregnant women diagnosed with early-onset preeclampsia and 34 healthy pregnant women were enrolled in this study. A mononuclear cell fragment from the venous blood was separated and frozen. The CD8+ and CD8- NK cell subpopulations were identified and compared to their immune checkpoint molecule expressions using multicolor flow cytometry. The serum CD226 levels were measured by ELISA. Based on our measures, the frequency of the CD8- subpopulation was significantly higher than that of the CD8+ counterpart in both the NKdim and NKbright subsets. Significantly lower CD226 surface expressions were detected in the preeclamptic group compared to healthy women in all the investigated subpopulations. However, while no difference was observed in the level of the soluble CD226 molecule between the two groups, the CD112 and CD155 surface expressions were significantly different. Our study\'s findings underscore the significant role of the CD8+ and CD8- NK subpopulations in the Th1-dominated immune environment. This deepens our understanding of early-onset preeclampsia and suggests that each subpopulation could contribute to the compensation mechanisms and the restoration of the immunological balance in this condition, a crucial step toward developing effective interventions.
摘要:
尽管对早发型先兆子痫的临床方面进行了大量研究,我们对胎盘发育不充分的免疫学后果的理解仍然不完整.早发型先兆子痫的Th1优势特征显著影响母体免疫耐受,免疫检查点分子在这些机制中的作用尚未完全阐明。我们的研究旨在填补这些关键的知识空白。本研究共纳入34例诊断为早发型先兆子痫的孕妇和34例健康孕妇。将来自静脉血的单核细胞片段分离并冷冻。使用多色流式细胞术鉴定CD8+和CD8-NK细胞亚群并与其免疫检查点分子表达进行比较。通过ELISA测量血清CD226水平。根据我们的措施,在NKdim和NKbright亚群中,CD8-亚群的频率均显著高于CD8+亚群.在所有研究的亚群中,与健康女性相比,在先兆子痫组中检测到显著更低的CD226表面表达。然而,而两组间可溶性CD226分子水平无差异,CD112和CD155表面表达差异显著。我们的研究结果强调了CD8+和CD8-NK亚群在Th1型免疫环境中的重要作用。这加深了我们对早发型先兆子痫的理解,并表明每个亚群都可能有助于这种情况下的补偿机制和免疫平衡的恢复。这是制定有效干预措施的关键一步。
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