Preeclampsia is Associated with Lower Percentages of Regulatory T Cells in Maternal Blood

Prins, Jelmer R.; Boelens, Hendrik M.; Heimweg, Janneke; Heide, S. van der; Dubois, Anthony; Oosterhout, Antoon J. van; Erwich, Jan Jaap H. M.

doi:10.1080/10641950802601237

Cited by 135 publications

(116 citation statements)

References 40 publications

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“…When defined as CD4 + CD25 + ⁄ high , preeclamptic women showed reduced circulating Treg numbers 110,111 or levels similar 112,113 to those of healthy pregnant women. Studies using FOXP3 protein as Treg marker support the notion of reduced Treg numbers 88,[114][115][116] in preeclampsia. In one report, the lower Treg number was accompanied by an increase in Th17 cells.…”

Section: Treg Cells In the Complications Of Pregnancymentioning

confidence: 87%

Regulatory T Helper Cells in Pregnancy and their Roles in Systemic versus Local Immune Tolerance

Ernerudh¹,

Berg²,

Mjösberg³

2011

American J Rep Immunol

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Problem During pregnancy, the maternal immune system needs to adapt in order not to reject the semi-allogenic fetus. Method In this review, we describe and discuss the role of regulatory T (Treg) cells in fetal tolerance. Results Treg cells constitute a T helper lineage that is derived from thymus (natural Treg cells) or is induced in the periphery (induced Treg cells). Treg cells are enriched at the fetal-maternal interface, showing a suppressive phenotype. In contrast, Treg cells are not increased in the circulation of pregnant women, and the suppressive capacity is similar to that in nonpregnant women. However, aberrations in Treg frequencies and functions, both systemically and in the uterus, may be involved in the complications of pregnancy. Conclusion Treg cells seem to have distinguished roles locally versus systemically, based on their distribution and phenotype.

This is the authors’ version of the publication: Jan Ernerudh, Göran Berg and Jenny Mjösberg, Regulatory T Helper Cells in Pregnancy and their Roles in Systemic versus Local Immune Tolerance, 2011, AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, (66), 31-43. http://dx.doi.org/10.1111/j.1600-0897.2011.01049.x Copyright: John Wiley and Sons http://www.wiley.com/

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Section: Treg Cells In the Complications Of Pregnancymentioning

confidence: 87%

Regulatory T Helper Cells in Pregnancy and their Roles in Systemic versus Local Immune Tolerance

Ernerudh¹,

Berg²,

Mjösberg³

2011

American J Rep Immunol

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“…During healthy pregnancy, the maternal immune system adapts to allow survival of a partially histoincompatible fetus, and failure of this adaptation contributes to poor placental invasion that predates the clinical onset of preeclampsia. Studies have suggested that impaired expansion of inducible Treg (iTreg) cells (40,51), particularly in the decidua, might represent a pathogenic defect in preeclampsia. A key feature of the niT-cell population that we describe is its ability to produce IL-17.…”

Section: Discussionmentioning

confidence: 99%

Neutrophils induce proangiogenic T cells with a regulatory phenotype in pregnancy

Nadkarni

Sferruzzi‐Perri

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

120

117

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Although neutrophils are known to be fundamental in controlling innate immune responses, their role in regulating adaptive immunity is just starting to be appreciated. We report that human neutrophils exposed to pregnancy hormones progesterone and estriol promote the establishment of maternal tolerance through the induction of a population of CD4+ T cells displaying a GARP+CD127loFOXP3+ phenotype following antigen activation. Neutrophil-induced T (niT) cells produce IL-10, IL-17, and VEGF and promote vessel growth in vitro. Neutrophil depletion during murine pregnancy leads to abnormal development of the fetal-maternal unit and reduced empbryo development, with placental architecture displaying poor trophoblast invasion and spiral artery development in the maternal decidua, accompanied by significantly attenuated niT cell numbers in draining lymph nodes. Using CD45 congenic cells, we show that induction of niT cells and their regulatory function occurs via transfer of apoptotic neutrophil-derived proteins, including forkhead box protein 1 (FOXO1), to T cells. Unlike in women with healthy pregnancies, neutrophils from blood and placental samples of preeclamptic women fail to induce niT cells as a direct consequence of their inability to transfer FOXO1 to T cells. Finally, neutrophil-selective FOXO1 knockdown leads to defective placentation and compromised embryo development, similar to that resulting from neutrophil depletion. These data define a nonredundant function of neutrophil–T cell interactions in the regulation of vascularization at the maternal–fetal interface.

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“…This is more important since findings of the numbers of Treg cells during preeclampsia are conflicting. Some authors show that in preeclampsia the numbers of circulating Treg cells are decreased compared with healthy pregnant women (Darmochwal-Kolarz et al 2012;Prins et al 2009) while others did not find different numbers of Treg cells between preeclamptic patients and normal pregnant women (Hu et al 2008;Paeschke et al 2005). Some of the inconsistencies regarding Treg cells may refer to how they were defined (Mjosberg et al 2009).…”

Section: Pregnancy-induced Changes In the Systemic Adaptive Immune Rementioning

confidence: 99%

The Placenta in Toxicology. Part II

et al. 2013

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During pregnancy, the maternal immune system is challenged by the semiallogeneic fetus, which must be tolerated without compromising fetal or maternal health. This review updates the systemic and local immune changes taking place during human pregnancy, including some examples in rodents. Systemic changes are induced by contact of maternal blood with placental factors and include enhanced innate immunity with increased activation of granulocytes and nonclassical monocytes. Although a bias toward T helper (Th2) and regulatory T cell (Treg) immunity has been associated with healthy pregnancy, the relationship between different circulating Th cell subsets is not straightforward. Instead, these adaptations appear most evidently at the fetal-maternal interface, where for instance Tregs are enriched and promote fetal tolerance. Also innate immune cells, that is, natural killer cells and macrophages, are enriched, constituting the majority of decidual leukocytes. These cells not only contribute to immune regulation but also aid in establishing the placenta by promoting trophoblast recruitment and angiogenesis. Thus, proper interaction between leukocytes and placental trophoblasts is necessary for normal placentation and immune adaptation. Consequently, spontaneous maladaptation or interference of the immune system with toxic substances may be important contributing factors for the development of pregnancy complications such as preeclampsia, preterm labor, and recurrent miscarriages.

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Preeclampsia is Associated with Lower Percentages of Regulatory T Cells in Maternal Blood

Cited by 135 publications

References 40 publications

Regulatory T Helper Cells in Pregnancy and their Roles in Systemic versus Local Immune Tolerance

Regulatory T Helper Cells in Pregnancy and their Roles in Systemic versus Local Immune Tolerance

Neutrophils induce proangiogenic T cells with a regulatory phenotype in pregnancy

The Placenta in Toxicology. Part II

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