Higher decidual EBI3 and HLA-G mRNA expression in preeclampsia: Cause or consequence of preeclampsia

Prins, Jelmer R.; Hoorn, Marie-Louise van der; Keijser, Remco; Ris‐Stalpers, Carrie; Beelen, Els van; Afink, Gijs B.; Claas, Frans H.J.; Post, Joris A. M. van der; Scherjon, Sicco A.

doi:10.1016/j.humimm.2015.10.004

Cited by 7 publications

(5 citation statements)

References 21 publications

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“…Previous studies reported that HLA-G + /CD4 + and HLA-G + /CD8 + Tregs were significantly lower in PE women, and HLA-G expression in placenta was decreased in RPL women [59][60][61]. Our study showed that HLA-G + /CD4 + Tregs in 1st trimester RPL and 2nd trimester GDM women as well as HLA-G + /CD8 + Tregs in 2nd and 3rd trimester GDM women were lower than those in normal pregnant women.…”

Section: Discussionsupporting

confidence: 52%

The Fluctuation of Regulatory T Cells during Pregnancy and Obstetrical Complications

Zhao

Bao

et al. 2020

Preprint

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Background: Regulatory T cells (Tregs) are critical immunomodulators during pregnancy by preventing maternal T-cell activation against fetal cells. However, how characteristics of maternal Tregs vary during pregnancy is still unclear. We analyzed the proportion and phenotypic characteristics of peripheral blood Tregs in normal pregnant women, women with recurrent pregnancy loss (RPL) or gestational diabetes mellitus (GDM), and non-pregnant women.Methods: We investigated the proportion of CD4+ Tregs, CD8+ Tregs and the expression of PD-1, GITR, HLA-G and CTLA-4 on them in the peripheral blood of normal pregnancies during 1st (n = 28), 2nd (n = 43), and 3rd trimester (n = 33); In addition, we evaluated pregnancies in the 1st trimester complicated by RPL (n = 21), in the 2nd (n = 17) and 3rd trimester (n = 28) complicated by GDM. Non-pregnant women (n = 57) were also investigated using flow cytometry.Results: During normal pregnancy, the proportion of CD4+ Tregs in all trimester and CD8+ Tregs in 2nd and 3rd trimester were higher(P ＜ 0.05，respectively) compared with non-pregnancy women. Moreover, the proportion of CD4+ Tregs was higher in 2nd trimester compared to 1st and 3rd trimester (P ＜ 0.01) while the proportion of CD8+ Tregs was higher in 3rd trimester compared to 1st and 2nd trimester (P ＜ 0.05). Compared to non-pregnant studies, the proportion of GITR+/CD8+ Tregs and HLA-G+/CD8+ Tregs in all trimester were higher(P ＜ 0.05, respectively). Moreover, the proportion of PD-1+/CD4+ Tregs, GITR+/CD4+ Tregs, PD-1+/CD8+ Tregs and CTLA-4+/CD8+ Tregs in 3rd trimester were significantly higher compared to 1st, 2nd trimester and non-pregnant group(P ＜ 0.05, respectively).In RPL and GDM groups, the proportions of CD4+ Tregs in all trimesters were decreased while the proportions of CD8+ Tregs in all trimesters were increased compared to normal pregnant group (P ＜ 0.05，respectively).In RPL group, the proportion of PD-1+/CD4+ Tregs, GITR+/CD4+ Tregs and HLA-G+/CD4+ Tregs were decreased compared to 1st trimester normal pregnant group (P ＜ 0.05，respectively). In 2nd trimester GDM group, the proportion of HLA-G+/CD4+ Tregs were decreased compared to 2nd trimester normal pregnant group (P ＜ 0.05，respectively). In 3rd trimester GDM group, the proportion of PD-1+/CD4+ Tregs, GITR+/CD4+ Tregs, PD-1+/CD8+ Tregs, GITR+/CD8+ Tregs and HLA-G+/CD8+Tregs were decreased compared to 3rd trimester normal pregnant group (P ＜ 0.05, respectively).Conclusions: The proportion of CD4+ Tregs and CD8+ Tregs increased during pregnancy, the proportions and subsets of CD4+ Tregs decreased and those of CD8+ Tregs increased in pregnancies complicated by RPL and GDM, indicating that regulatory T cells play a role in pregnancy maintenance, and the abnormal expression of Tregs might be related to the complicated pregnancy.

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Section: Discussionsupporting

confidence: 52%

The Fluctuation of Regulatory T Cells during Pregnancy and Obstetrical Complications

Zhao

Bao

et al. 2020

Preprint

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“…37 Higher decidual EBI3 mRNA expression has also been found in PE compared to normotensive pregnancies. 38 Overall, these studies suggest that dysregulation of IL-27 and IL-27 receptor (WSX-1) is relevant to PE.…”

Section: Discussionmentioning

confidence: 90%

Interleukin-27 Inhibits Trophoblast Cell Invasion and Migration by Affecting the Epithelial—Mesenchymal Transition in Preeclampsia

Yin

Han

et al. 2019

Reprod. Sci.

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Preeclampsia (PE) is a pregnancy-specific disorder representing a major cause of maternal and perinatal morbidity and mortality. Invasive and migratory phenotypes are acquired by trophoblasts through the process of epithelial–mesenchymal transition (EMT). Studies have shown that trophoblast EMT events are dysregulated in PE and play an important role in its development. Dysregulation of interleukin (IL)-27 and IL-27R (T-cell cytokine receptor (TCCR)/WSX -1) is relevant to PE. In this study, our results demonstrated that IL-27 did not significantly affect the proliferation and apoptosis of HTR -8/SVneo trophoblast cells, while it did significantly inhibit trophoblast invasion and migration. The expression of EMT-related proteins in HTR-8/SVneo cells and extravillous explants was detected after treatment with IL-27. Expression of epithelial markers was increased, and mesenchymal marker expression was reduced. Furthermore, we found that IL-27 could induce significant phosphorylation of Signal Transducer and Activator of Transcription 1 (STAT1) and Signal Transducer and Activator of Transcription 3 (STAT3) in a time-dependent manner in HTR-8/SVneo cells. Selective inhibitors of STAT1 (STAT1 siRNA) and STAT3 (STAT3 siRNA) were used to determine whether both STAT1 and STAT3 are required for IL-27-mediated inhibition of EMT. STAT1 inhibition in IL-27-treated cells attenuated the IL-27 effect, while the inhibition of STAT3 activation had no effect on the development of the epithelial phenotype. These results demonstrate that IL-27 may inhibit trophoblast cell migration and invasion by affecting the EMT process through an STAT1-dominant pathway in PE.

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“…An in vitro study indicated that p35 and EBI‐3 mRNAs were decreased in the decidua of PE placentas, while only EBI‐3 was downregulated within the chorionic layer . On the contrary, in a small pilot study, higher mRNA levels of EBI3 were observed in decidual lymphocytes and macrophages of PE pregnancies.…”

Section: Resultsmentioning

confidence: 67%

The role of interleukins in preeclampsia: A comprehensive review

Bellos

Karageorgiou

Kapnias

et al. 2018

American J Rep Immunol

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Preeclampsia is a multi‐system hypertensive disorder of pregnancy, with significant rates of maternal and neonatal morbidity. It represents a major cause of preterm birth, as definitive treatment demands fetal delivery. Although its pathophysiology is complicated, placental hypoxia and endothelial dysfunction constitute established pathogenetic steps of the disease. Inflammation is considered to be a crucial mediator of preeclampsia process, as an imbalance between TH1, TH2, and TH17 immune responses is observed. The present review accumulates current knowledge about the contribution of interleukins in preeclampsia, summarizing the pathways through which each interleukin exerts its function in the disease. Also, the role of genetic polymorphisms is explored and the predictive efficacy of maternal serum interleukin levels is evaluated. Finally, recommendations about the safe interpretation of the outcomes, as well as guidance for future research, are provided.

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Higher decidual EBI3 and HLA-G mRNA expression in preeclampsia: Cause or consequence of preeclampsia

Cited by 7 publications

References 21 publications

The Fluctuation of Regulatory T Cells during Pregnancy and Obstetrical Complications

The Fluctuation of Regulatory T Cells during Pregnancy and Obstetrical Complications

Interleukin-27 Inhibits Trophoblast Cell Invasion and Migration by Affecting the Epithelial—Mesenchymal Transition in Preeclampsia

The role of interleukins in preeclampsia: A comprehensive review

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