4.5 Article

Preeclampsia-Derived Exosomes Imbalance the Activity of Th17 and Treg in PBMCs from Healthy Pregnant Women

Journal

REPRODUCTIVE SCIENCES
Volume 30, Issue 4, Pages 1186-1197

Publisher

SPRINGER HEIDELBERG
DOI: 10.1007/s43032-022-01059-x

Keywords

Pre-eclampsia; Exosomes; Regulatory T cells; T helper 17 cells

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This study identifies the impact of preeclampsia (PE) exosomes on the activity of Th17 and Treg cells and their related gene expression and cytokine profiles in healthy pregnant women. PE patients exhibited decreased Treg cell number and increased Th17 cells, while intervention with PE exosomes led to significant changes in gene expression and cytokine levels. These findings suggest a possible role of PE exosomes in the pathogenesis of PE.
The disturbance of maternofetal immune tolerance is identified as one of the important issues in the pathology of preeclampsia (PE). PE exosomes are believed to possess significant roles in immune abnormalities. In this study, to assess the possible effects of PE exosomes in the pathophysiology of preeclampsia patients, exosomes were isolated from the serum of PE patients and incubated with peripheral blood mononuclear cells (PBMCs) of healthy pregnant women. Also, exosomes from healthy pregnant women were utilized as the control. Th17/Treg ratio in PE and healthy pregnant women and the effects of PE exosomes on expression level of Th17 and Treg transcription factors, as well as their related cytokines in PBMCs of healthy pregnant women, were evaluated. A significant decrease in Treg cell number and increase in Th17 cells and Th17/Treg ratio were observed in PE patients. Following PE-exosome intervention, a significant increase in mRNA expression level of ROR gamma t, IL-17, IL-23, IL-1 beta, and IL-6, and significant decrease in IL-10 and TGF beta were evident. On the other hand, no significant difference in FoxP3 level was detected. Additionally, increased IL-6, IL-17, IL-23, and IL-1 beta levels and decreased IL-10 level in the supernatant of cultured PBMCs from healthy pregnant women following PE-exosome intervention were exhibited. However, TGF-beta level did not change significantly. Based on our findings, PE exosomes are able to alter the activity of Th17 and Treg cells as well as their related gene expression and cytokine profiles. These findings support the probable role of PE exosomes in PE pathogenesis.

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