T lymphocytes and preeclampsia: The potential role of T‐cell subsets and related MicroRNAs in the pathogenesis of preeclampsia

Zolfaghari, Mohammad Ali; ArefNezhad, Reza; Parhizkar, Forough; Hejazi, Mohammad Saeid; Khiavi, Farhad Motavalli; Mahmoodpoor, Ata; Yousefi, Mehdi

doi:10.1111/aji.13475

Cited by 19 publications

(13 citation statements)

References 142 publications

(233 reference statements)

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“…In particular, T reg cells exert immune tolerance functions by mechanisms including antigen presentation, secretion of inhibitory cytokines and cytolysis of target cells 152,153 . Abnormal release of T reg cell factors, including cytokines and microRNA, is found in pre-eclampsia 154 . Epidemiological studies support experimental data reporting that the maternal immune response to paternally derived antigens on the trophoblast 155 is decreased by previous exposure to seminal fluid 156 : a higher incidence of pre-eclampsia is found in primiparity, pregnancies in which the paternity has changed, pregnancies after a prolonged inter-pregnancy interval (>10 years), pregnancies conceived soon after first coitus, and pregnancies conceived with the use of donor egg 157 and sperm 90 .…”

Section: Primermentioning

confidence: 99%

Pre-eclampsia

Dimitriadis

Rolnik

Zhou

et al. 2023

Nat Rev Dis Primers

265

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Pre-eclampsia is a life-threatening disease of pregnancy unique to humans and a leading cause of maternal and neonatal morbidity and mortality. Women who survive pre-eclampsia have reduced life expectancy, with increased risks of stroke, cardiovascular disease and diabetes, while babies from a pre-eclamptic pregnancy have increased risks of preterm birth, perinatal death and neurodevelopmental disability and cardiovascular and metabolic disease later in life. Preeclampsia is a complex multisystem disease, diagnosed by sudden-onset hypertension (>20 weeks of gestation) and at least one other associated complication, including proteinuria, maternal organ dysfunction or uteroplacental dysfunction. Pre-eclampsia is found only when a placenta is or was recently present and is classified as preterm (delivery <37 weeks of gestation), term (delivery ≥37 weeks of gestation) and postpartum pre-eclampsia. The maternal syndrome of pre-eclampsia is driven by a dysfunctional placenta, which releases factors into maternal blood causing systemic inflammation and widespread maternal endothelial dysfunction. Available treatments target maternal hypertension and seizures, but the only 'cure' for pre-eclampsia is delivery of the dysfunctional placenta and baby, often prematurely. Despite decades of research, the aetiology of pre-eclampsia, particularly of term and postpartum pre-eclampsia, remains poorly defined. Significant advances have been made in the prediction and prevention of preterm pre-eclampsia, which is predicted in early pregnancy through combined screening and is prevented with daily low-dose aspirin, starting before 16 weeks of gestation. By contrast, the prediction of term and postpartum pre-eclampsia is limited and there are no preventive treatments. Future research must investigate the pathogenesis of pre-eclampsia, in particular of term and postpartum pre-eclampsia, and evaluate new Nature Reviews Disease Primers | (2023) 9:8 2 0123456789();: Primer Epidemiology Incidence and mortalityThe global prevalence of all pre-eclampsia in the years 2002-2010 was estimated at 4.6% of deliveries but reported regional rates varied between 1% and 5.6% 14 . Where reported, the prevalence of preterm pre-eclampsia is <1% [15][16][17][18] . The prevalence of pre-eclampsia is generally reported as lower in low-income and middle-income countries (LMICs) (except sub-Saharan Africa) than in high-income countries (HICs) 19,20 ; however, it is likely that differences in classification, access to prenatal care and under-reporting in LMICs affect prevalence data 20,21 . Furthermore, most pre-eclampsia research is performed in HICs, potentially leading to bias and generalizability concerns in the populations sampled and the research questions asked.Hypertensive disorders of pregnancy (including pre-eclampsia) are the second most common cause (behind haemorrhage) of maternal Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rights...

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Section: Primermentioning

confidence: 99%

Pre-eclampsia

Dimitriadis

Rolnik

Zhou

et al. 2023

Nat Rev Dis Primers

265

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“…Human CD4+ T cells can be classified into Th1, Th2, regulatory T (Treg), and Th17 cells based on their pattern of cytokine production, and they display different biological functions [ 30 , 31 ]. Research has proposed that successful pregnancy is a Th2 type phenomenon, and Th1 type reactivity is harmful to pregnancy [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

The AHNAK induces increased IL-6 production in CD4+ T cells and serves as a potential diagnostic biomarker for recurrent pregnancy loss

Liu

Feng

et al. 2022

Clinical and Experimental Immunology

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Disorganized maternal–fetal immune tolerance contributes to the occurrence of unexplained recurrent pregnancy loss (RPL). AHNAK is a scaffolding protein participating in the regulation of Ca2+ entry into T cells and the pathophysiology of diverse diseases. We performed differential gene expression analysis in decidual immune cells (DICs) isolated from three patients with RPL and from three healthy controls via RNA-sequencing (RNA-seq), which revealed 407 differentially expressed genes (DEGs). Among these DEGs, we underscored the clinical significance of elevated AHNAK mRNA and protein levels in DICs, peripheral blood mononuclear cells (PBMCs), and decidua of the patients with RPL, suggesting its potential use as a biomarker for the diagnosis of RPL. Especially, the ratios of decidual and blood AHNAK+CD4+ T cells in the CD4+ T cell population were significantly increased in patients with RPL, and the loss of AHNAK was further shown to inhibit interleukin (IL)-6 secretion in the CD4+ Jurkat cell line. Similar patterns were also observed in the clinical decidual and blood specimens. We uncovered that the AHNAK+CD4+ T cells could secrete more IL-6 than that the corresponding AHNAK-CD4+ T cells. Moreover, the frequencies of decidual and blood IL-6+CD4+ T cells in the CD4+ T-cell population were also increased in patients with RPL and showed significant positive correlations with the frequencies of AHNAK+CD4+ T cells. Our findings suggest that the elevated AHNAK expressed by CD4+ T cells may be involved in the immune dysregulation of RPL by increasing IL-6 production, illustrating its potential as a novel intervention target for RPL.

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“…However, the balance between Th1/Th2 functions in peripheral blood and decidua changes toward a Th1-dominated inflammatory phenotype in preeclamptic patients ( 56 , 57 ). Th1 induced chronic inflammatory reactions in the fetal- maternal interface, placental damage and endothelial dysfunction by secreting the amounts of TNF-α, IFN-γ, IL- 1β, and IL- 12 ( 58 ).Preeclamptic symptoms such as elevated blood pressure, proteinuria and renal function abnormalities occur in pregnant mice after Th1 cell importation ( 59 ). A growing number of studies have found that disruption of Treg/Th17 balance can lead to the development of preeclampsia and that the balance between Treg and Th17 is essential for the prevention of preeclampsia.…”

Section: Discussionmentioning

confidence: 99%

Global trends in research of immune cells associated with hypertensive disorders of pregnancy: A 20-year bibliometric analyses (from 2001 to 2021)

Wang

Tong

2023

Front. Immunol.

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BackgroundA growing evidence suggests that immune cells play a significant role in the pathogenesis of hypertensive disorders of pregnancy (HDP).Over the past 20 years, several studies have been conducted on the role of immune cells in hypertensive disorders of pregnancy. This study used bibliometric analysis to assess research hotspots and future trends in studies on immune cells in hypertensive disorders of pregnancy.MethodsWe extracted all relevant literature on immune cells and hypertensive disorders of pregnancy from the Web of Science core collection for the period of 2001 to 2021. We used VOS Viewer, CiteSpace, R-bibliometrix and Python for bibliometric analysis.ResultsWe identified 2,388 records published in 593 journals by 9,886 authors from 2,174 universities/institutions in 91 countries/regions. The number of publications tended to increase over time, with the highest number of publications in 2021, up to 205. The USA was the country with the most publications. UNIVERSITY OF MISSISSIPPI was the most influential institution. Lamarca B, Romero R, and Saito S were the most prolific authors. Finally, three research hotspot clusters were identified based on keywords, which reflected the role of immune cells in the development of hypertensive disorders of pregnancy, the current research status,and predicted hot spots for future research.ConclusionsOur study systematically analyzed the role of immune cells in the pathogenesis of hypertensive disorders of pregnancy in the last 20 years. Our results indicated that immune cells, such as T cells, natural killer (NK) cells,and macrophages, and the cytokines released such as TNF-α, IFN-γ in the maternal circulation and at the maternal-fetal interface would influence the development of hypertensive disorders of pregnancy and we need further investigate the role of individual immune cells and translational studies to provide new therapeutic perspectives to mitigate adverse perinatal outcomes due to hypertensive disorders of pregnancy. In conclusion, bibliometric studies provide a general overview of immune cells in the study of hypertensive disorders of pregnancy.

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T lymphocytes and preeclampsia: The potential role of T‐cell subsets and related MicroRNAs in the pathogenesis of preeclampsia

Cited by 19 publications

References 142 publications

Pre-eclampsia

Pre-eclampsia

The AHNAK induces increased IL-6 production in CD4+ T cells and serves as a potential diagnostic biomarker for recurrent pregnancy loss

Global trends in research of immune cells associated with hypertensive disorders of pregnancy: A 20-year bibliometric analyses (from 2001 to 2021)

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