Interferon regulatory factor 1 mediated inhibition of Treg cell differentiation induces maternal-fetal immune imbalance in preeclampsia.

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.