Placental CD4+ T cells from preeclamptic patients cause autoantibodies to the angiotensin II type I receptor and hypertension in a pregnant rat model of preeclampsia

Reeve, Kristin E.; Deer, Evangeline; Amaral, Lorena M.; Cornelius, Denise C.; Herrock, Owen; Harmon, Ashlyn C.; Campbell, Nathan; Fitzgerald, Sarah; Ibrahim, Tarek; Wallukat, Gerd; Dechend, Ralf; LaMarca, Babbette

doi:10.37349/emed.2022.00077

Cited by 10 publications

(9 citation statements)

References 34 publications

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“…We have also shown that T cells isolated from patients with PE can cause PE symptoms in pregnant nude-athymic rats (75). More recently, we showed that incubation with anti-CD40L before adoptive transfer also improved PE symptoms in the nude-athymic model, further indicating that T cells costimulating B cells is critical to the pathophysiology of PE (64).…”

Section: T Cells In Normal Pregnancy and Preeclampsiamentioning

confidence: 87%

“…Studies also demonstrate that inflammatory cytokines, such as TNF- α , IL-6, and IL-17, play crucial roles in immune activation by increasing the production of vasoactive molecules, such as AT1-AA, ET-1, and sFlt-1 (61 –63). Importantly we recently showed that adoptive transfer of CD4+ T cells from placentas of patients with PE causes hypertension; intrauterine growth retardation; and increased AT1-AA, sFlt-1, ET-1, and the cytokines TNF- α and IL-17, demonstrating the importance of T cells in causing many characteristics of PE (64).…”

Section: T Cells In Normal Pregnancy and Preeclampsiamentioning

confidence: 99%

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The Role of Different Lymphoid Cell Populations in Preeclampsia Pathophysiology

et al. 2022

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Preeclampsia (PE), new-onset hypertension during pregnancy, affects up to 10% of pregnancies worldwide. Despite being the leading cause of maternal and fetal morbidity and mortality, there is no cure for PE beyond the delivery of the fetal-placental unit. Although the exact pathogenesis of PE is unclear, there is a strong correlation between chronic immune activation, intrauterine growth restriction, uterine artery resistance, dysregulation of the renin angiotensin system which contributes to renal dysfunction, and the resulting hypertension during pregnancy. The genesis of PE is thought to begin with insufficient trophoblast invasion leading to reduced spiral artery remodeling resulting in decreased placental perfusion thereby causing placental ischemia. The ischemic placenta releases factors that shower the endothelium and contribute to peripheral vasoconstriction and chronic immune activation and oxidative stress. Studies have shown imbalances in pro-inflammatory and anti-inflammatory cell types in women with PE and in animal models utilized to examine mediators of a PE phenotype during pregnancy. T cells, B cells, and natural killer cells have all emerged as potential mediators contributing to the production of vasoactive factors, renal and endothelial dysfunction, mitochondrial dysfunction, and hypertension during pregnancy. The chronic immune activation seen in PE leads to a higher risk for other diseases such as cardiovascular disease, chronic kidney disease, dementia during their postpartum period, and PE during a subsequent pregnancy. The purpose of this review is to highlight studies demonstrating the role that different lymphoid cell populations play in the pathophysiology of PE. Moreover, we will discuss treatments focused on restoring immune balance or targeting specific immune mediators that may be potential strategies to improve maternal and fetal outcomes associated with PE.

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Section: T Cells In Normal Pregnancy and Preeclampsiamentioning

confidence: 87%

Section: T Cells In Normal Pregnancy and Preeclampsiamentioning

confidence: 99%

The Role of Different Lymphoid Cell Populations in Preeclampsia Pathophysiology

et al. 2022

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“…We have demonstrated the importance of T cell‐B cell communication as an important step in the pathophysiology of hypertension and AT1‐AA production in the RUPP rat model of placental ischemia 20,21 . T cell‐B cell communication is a pivotal step in B cell activation and formation of immune memory, 22 allowing for long‐term production of antibodies after antigen exposure.…”

Section: Introductionmentioning

confidence: 94%

“…We have demonstrated the importance of T cell-B cell communication as an important step in the pathophysiology of hypertension and AT1-AA production in the RUPP rat model of placental ischemia. 20,21 T cell-B cell communication is a pivotal step in B cell activation and formation of immune memory, 22 allowing for long-term production of antibodies after antigen exposure. We have shown that B cell depletion with Rituximab attenuates the hypertension associated with placental ischemia in the RUPP preclinical model of placental ischemia; therefore, implicating a role for B cells in PE pathophysiology.…”

Section: Introductionmentioning

confidence: 99%

Inhibiting B cell activating factor attenuates preeclamptic symptoms in placental ischemic rats

Herrock

Deer

Amaral

et al. 2023

American J Rep Immunol

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Problem Preeclampsia (PE), new‐onset hypertension during pregnancy, is associated with a pro‐inflammatory state with activated T cells, cytolytic natural killer (NK) cells, dysregulated complement proteins, and B cells secreting agonistic autoantibodies to the angiotensin II type‐1 receptor (AT1‐AA). The reduced uterine perfusion pressure (RUPP) model of placental ischemia recapitulates these features of PE. Blocking CD40L‐CD40 communication between T and B cells or B cell depletion with Rituximab prevents hypertension and AT1‐AA production in RUPP rats. This suggests that T cell‐dependent B cell activation contributes to the hypertension and AT1‐AA associated with PE. B2 cells maturing into antibody producing plasma cells are the product of T cell‐dependent B cell‐interactions and B cell Activating Factor (BAFF) is an integral cytokine in the development of B2 cells specifically. Thus, we hypothesize that BAFF blockade will selectively deplete B2 cells, therefore reducing blood pressure, AT1‐AA, activated NK Cells, and complement in the RUPP rat model of PE. Method of study Gestational Day (GD) 14 pregnant rats underwent the RUPP procedure, and a subset were treated with 1 mg/kg Anti‐BAFF antibodies via jugular catheters. On GD19, blood pressure was measured, B cells and NK cells were measured by flow cytometry, AT1‐AA was measured by cardiomyocyte bioassay, and complement activation was measured by ELISA. Results Anti‐BAFF therapy attenuated hypertension, AT1‐AA, NK cell activation, and APRIL levels in RUPP rats without negatively impacting fetal outcomes. Conclusions This study demonstrates that B2 cells contribute to hypertension, AT1‐AA, and NK cell activation in response to placental ischemia during pregnancy.

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“…Our lab has shown that Th cells stimulated by placental ischemia from rats or humans induce hypertension, mitochondrial dysfunction, sflt-1, AT1-AA, and other features of PE in pregnant rats (Deer et al, 2021;Reeve et al, 2022). However, blockade of communication between Th cells and B cells prevents the features of PE induced by Th cell adoptive transfer (Cornelius et al, 2015).…”

Section: T Helper Cells and B Cells In Preeclampsiamentioning

confidence: 99%

Setting a stage: Inflammation during preeclampsia and postpartum

2023

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Preeclampsia (PE) is a leading cause of maternal and fetal mortality worldwide. The immune system plays a critical role in normal pregnancy progression; however, inappropriate inflammatory responses have been consistently linked with PE pathophysiology. This inflammatory phenotype consists of activation of the innate immune system, adaptive immune system, and increased inflammatory mediators in circulation. Moreover, recent studies have shown that the inflammatory profile seen in PE persists into the postpartum period. This manuscript aims to highlight recent advances in research relating to inflammation in PE as well as the inflammation that persists postpartum in women after a PE pregnancy. With the advent of the COVID-19 pandemic, there has been an increase in obstetric disorders associated with COVID-19 infection during pregnancy. This manuscript also aims to shed light on the relationship between COVID-19 infection during pregnancy and the increased incidence of PE in these women.

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Placental CD4+ T cells from preeclamptic patients cause autoantibodies to the angiotensin II type I receptor and hypertension in a pregnant rat model of preeclampsia

Cited by 10 publications

References 34 publications

The Role of Different Lymphoid Cell Populations in Preeclampsia Pathophysiology

The Role of Different Lymphoid Cell Populations in Preeclampsia Pathophysiology

Inhibiting B cell activating factor attenuates preeclamptic symptoms in placental ischemic rats

Setting a stage: Inflammation during preeclampsia and postpartum

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