Study on the mechanism of microRNA-210 regulating the immune pathogenesis of Treg cells in preeclampsia

Objective The aim of this study was to evaluate the number of Treg cells in preeclampsia (PE) patients, to explore the expression levels of microRNA-210 (microRNA-210) and forkhead box p3 (Foxp3) genes in preeclampsia, and to reveal the regulatory mechanism of microRNA-210 and Foxp3 in preeclampsia. Methods Serum levels of cytokines [interleukin (IL)-6, IL-10, IL-17, and transforming growth factor-beta 1 (TGF-β1)] were detected with enzyme-linked immunosorbent assay (ELISA). 29 patients with late-onset preeclampsia (≥36 weeks of gestation), 27 pregnant women with normal uncomplicated pregnancies (≥36 weeks of gestation) and 20 healthy non-pregnant women were enrolled in the study. Reverse-transcription polymerase chain reaction (qRT-PCR) was performed to detect mRNA expression for maternal placenta retinoic acid-related orphan receptor C (RORc), Foxp3, and miR-210. Foxp3 protein expression was evaluated by Western blot. Results ⑴ The serum levels of IL-6, IL-17 and TGF-beta 1 in preeclampsia patients were significantly higher than those in normal pregnant women, and the level of Treg cytokine IL-10 was lower than that in normal pregnant women (P<0.05). ⑵ The percentage of CD4+ CD25+ CD127-/CD4+ T cells in peripheral blood of preeclampsia patients was significantly lower than that of normal pregnancy group and healthy non-pregnant women (P<0.001). ⑶ The mRNA expression of Foxp3 in placenta of preeclampsia patients was significantly lower than that of normal pregnant women, RORc in preeclampsia patients was significantly higher than that of normal pregnant women, and the expression of microRNA210 in preeclampsia patients was enhanced (P<0.01). ⑷ Consistent with mRNA expression results, lower protein expression levels of Foxp3 was observed in patients with PE compared with normal pregnant subjects. Conclusions Treg cells decreased in preeclampsia patients and Treg/Th17 imbalance existed in preeclampsia patients, which regulate maternal immune tolerance to fetuses. The expression of Foxp3 in placenta of preeclampsia patients was significantly decreased, which was correlated with the expression of microRNA-210. Key words: MicroRNAs; T-lymphocytes, regulatory; Pre-eclampsia; Forkhead transcription factors