干扰素调节因子 1 介导的 Treg 细胞分化抑制会导致先兆子痫的母胎免疫失衡。
Interferon regulatory factor 1 mediated inhibition of Treg cell differentiation induces maternal-fetal immune imbalance in preeclampsia.
发表日期:2024 Aug 29
作者:
Yue Ma, Shenglong Ye, Yuanying Liu, Xueqing Zhao, Yanling Wang, Yongqing Wang
来源:
INTERNATIONAL IMMUNOPHARMACOLOGY
摘要:
成功妊娠的建立和维持在很大程度上依赖于母胎免疫耐受。妊娠期间的炎症和免疫机制与肿瘤进展中观察到的相似,Treg 细胞在两种情况下都表现出相似的免疫调节功能。干扰素调节因子 1 (IRF1) 参与调节肿瘤内的免疫环境并影响调节性 T (Treg) 细胞分化。然而,IRF1 与先兆子痫 (PE) 发病之间的确切关联仍不清楚。在我们的研究中,我们通过免疫荧光分析确定滋养层是母胎界面 IRF1 表达的重要来源。此外,在PE患者的胎盘组织和外周血样本中检测到IRF1表达水平升高,同时Th17/Treg比率失衡。在外周循环中,IRF1 mRNA 水平和 Foxp3 mRNA(一种 Treg 细胞特异性转录因子)之间观察到显着的负相关。 IRF1 mRNA 表达与收缩压呈正相关,与血清白蛋白水平呈负相关。此外,将幼稚 T 细胞与过表达 IRF1 的 HTR-8/SV neo 细胞上清液共培养,会导致 T 细胞向 Treg 细胞的分化减少。总之,我们的研究表明,PE 患者的外周血和滋养层细胞中 IRF1 表达升高。滋养层细胞中 IRF1 升高会阻碍母体 Treg 细胞的分化,破坏母胎免疫耐受并导致 PE 发病机制。此外,IRF1 表达与疾病严重程度相关,表明其作为 PE 中新型敏感靶点的潜力。版权所有 © 2024 Elsevier B.V. 保留所有权利。
The establishment and maintenance of a successful pregnancy rely heavily on maternal-fetal immune tolerance. Inflammatory and immune mechanisms during pregnancy bear a resemblance to those observed in tumor progression, with Treg cells exhibiting similar immunoregulatory functions in both contexts. Interferon regulatory factor 1 (IRF1) is implicated in modulating the immune milieu within tumors and influencing regulatory T (Treg) cell differentiation. However, the precise association between IRF1 and the onset of preeclampsia (PE) remains unclear. In our investigation, we identified trophoblasts as a significant source of IRF1 expression at the maternal-fetal interface through immunofluorescence analysis. Moreover, heightened levels of IRF1 expression were detected in both placental tissues and peripheral blood samples obtained from PE patients, concomitant with an imbalance in the Th17/Treg ratio. In the peripheral circulation, a notable inverse correlation was observed between IRF1 mRNA levels and Foxp3 mRNA, a transcription factor specific to Treg cells. IRF1 mRNA expression showed a positive association with systolic blood pressure and a negative association with serum albumin levels. Furthermore, co-culturing naïve T cells with supernatants from HTR-8/SV neo cells overexpressing IRF1 resulted in diminished differentiation of T cells into Treg cells. In summary, our study indicates elevated IRF1 expression in the peripheral blood and trophoblast cells of PE patients. Elevated IRF1 in trophoblast cells hinders the differentiation of maternal Treg cells, disrupting maternal-fetal immune tolerance and contributing to PE pathogenesis. Additionally, IRF1 expression correlates with disease severity, suggesting its potential as a novel sensitive target in PE.Copyright © 2024 Elsevier B.V. All rights reserved.