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

<b>Background/Objectives:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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 (<i>p</i> < 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. <b>Conclusions:</b> 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.

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Publication Details

Journal
Journal of Clinical Medicine
Published
2025-10-15
DOI
https://doi.org/10.3390/jcm14207288
Citations
2
Primary Topic
Reproductive System and Pregnancy
Type
article
Field-Weighted Citation Impact
1.59

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article

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

Maciej Krasiński, Anna Kwaśniewska, Maciej Kwiatek, Tomasz Gęca et al.
2 citations
Journal of Clinical Medicine
Reproductive System and Pregnancy
1.59
article

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

Maciej Krasiński, Anna Kwaśniewska, Maciej Kwiatek, Tomasz Gęca, Maciej Brązert, Tomasz Kamil Urbanowicz, Magdalena Ewa Kowalkowska, Ewelina Grywalska, Wojciech Kwaśniewski, Sebastian Mertowski, Mansur Rahnama
article en
2 citations

Abstract

<b>Background/Objectives:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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 (<i>p</i> < 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. <b>Conclusions:</b> 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.

Journal of Clinical MedicineVol. 14(20)
Poznan University of Medical Sciences (PL), Medical University of Lublin (PL), Imperial College Healthcare NHS Trust (GB), University of Bydgoszcz (PL), St Mary's Hospital (GB), Collegium Medicum in Bydgoszcz (PL)
Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu, Uniwersytet Medyczny w Lublinie
Openalex Percentile: Top 14%
Reproductive System and Pregnancy
1.59
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