Dysregulation of Treg/Th17 Balance and Intracellular Expression of IL-21 and IL-22 in the Pathogenesis of Gestational Hypertension

Background/Objectives: Pregnancy-induced hypertension (PIH), including preeclampsia (PE), remains a significant cause of maternal and fetal morbidity. Immune imbalance involving T helper (Th17) and regulatory T (Treg) cells is increasingly recognized as contributing to the pathogenesis of PIH. This study aimed to assess the proportions of Th17 and Treg cells and intracellular cytokine expression (IL-17A, IL-17F, IL-21, and IL-22) in the peripheral blood of hypertensive versus normotensive pregnant women. Methods: A total of 108 pregnant women were included: 60 with hypertensive disorders and 48 normotensive controls. Peripheral blood mononuclear cells were analyzed using multiparametric flow cytometry to quantify CD4+CD25+FoxP3+ Treg and CD4+IL-17A+ Th17 cells, along with intracellular IL-17F, IL-21, and IL-22 co-expression. Correlations with clinical and obstetric parameters were evaluated. Results: Hypertensive patients showed significantly increased proportions of activated Th17 cells (CD4+IL-17A+) and Th17 subpopulations co-expressing IL-17F and IL-22, as well as IL-21 and IL-22 (p < 0.0001). Although Treg cell percentages were lower in the hypertensive group, the difference was not statistically significant. A pronounced Th17/Treg imbalance was observed. Positive correlations were found between Th17 subpopulations and gestational age, birth weight, and length, as well as maternal age. Conclusions: The immune profile in hypertensive pregnancies was characterized by a shift toward Th17-mediated proinflammatory responses, supporting the role of immune dysregulation in PIH. The increased frequency of Th17 cells co-expressing IL-21 and IL-22 may serve as a potential biomarker of disease severity and warrants further exploration.