Maternal Foxp3 Expressing CD4+ CD25+ and CD4+ CD25− Regulatory T‐Cell Populations are Enriched in Human Early Normal Pregnancy Decidua: A Phenotypic Study of Paired Decidual and Peripheral Blood Samples

Dimova, Tanya; Nagaeva, Olga; Stenqvist, Ann-Christin; Hedlund, Marie; Kjellberg, Lennart; Strand, Magnus; Dehlin, Eva; Mincheva‐Nilsson, Lucia

doi:10.1111/j.1600-0897.2011.01046.x

Cited by 81 publications

(81 citation statements)

References 48 publications

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“…In this study, we show, to our knowledge for the first time, an accumulation of GR-MDSCs with T cell suppressive capacities at the maternal-fetal interface of healthy pregnancies but a reduced accumulation in patients with spontaneous abortions. These results parallel data from others showing an enrichment of Tregs in human decidua and an association between diminished Treg accumulation and pregnancy failure (32,34,35). Recently, reduced MDSCs in peripheral blood of patients with early miscarriage and a depletion of MDSCs leading to pregnancy failure in mice have also been shown (36,37).…”

Section: Discussionsupporting

confidence: 77%

“…Genetic analysis verified that most GR-MDSCs isolated from placenta were maternal cells, and immunohistochemical staining of placenta revealed that most CD66b + cells were located on the maternal side, predominantly in the intervillous space and the decidual tissue. Immunohistochemical studies on Tregs at the maternal-fetal interface showed a similar distribution of these cells in decidual stroma (34). Because CD66b staining cannot distinguish between immature GR-MDSCs with suppressive capacities and mature granulocytes, these results have to be viewed with caution.…”

Section: Discussionmentioning

confidence: 96%

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Granulocytic Myeloid-Derived Suppressor Cells Accumulate in Human Placenta and Polarize toward a Th2 Phenotype

Köstlin

Hofstädter

Ostermeir

et al. 2016

The Journal of Immunology

101

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Tolerance induction toward the semiallogeneic fetus is crucial to enable a successful pregnancy; its failure is associated with abortion or preterm delivery. Skewing T cell differentiation toward a Th2-dominated phenotype seems to be pivotal in maternal immune adaption, yet underlying mechanisms are incompletely understood. Myeloid-derived suppressor cells (MDSCs) are innate immune cells that mediate T cell suppression and are increased in cord blood of healthy newborns and in peripheral blood of pregnant women. In this study, we demonstrate that granulocytic MDSCs (GR-MDSCs) accumulate in human placenta of healthy pregnancies but are diminished in patients with spontaneous abortions. Placental GR-MDSCs effectively suppressed T cell responses by expression of arginase I and production of reactive oxygen species and were activated at the maternal–fetal interface through interaction with trophoblast cells. Furthermore, GR-MDSCs isolated from placenta polarized CD4+ T cells toward a Th2 cytokine response. These results highlight a potential role of GR-MDSCs in inducing and maintaining maternal–fetal tolerance and suggest them as a promising target for therapeutic manipulation of pregnancy complications.

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Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 96%

Granulocytic Myeloid-Derived Suppressor Cells Accumulate in Human Placenta and Polarize toward a Th2 Phenotype

Köstlin

Hofstädter

Ostermeir

et al. 2016

The Journal of Immunology

101

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“…The Treg cells are not only enriched in the decidua, they also show a more pronounced suppressive phenotype than in blood with regard to expression of, for example, Foxp3, cytotoxic T lymphocyte antigen 4 (CTLA-4), CD25, and TGF-b (Dimova et al 2011;Mjosberg et al 2010). The recruitment of decidual T cells is governed by human chorionic gonadotropin (Schumacher et al 2009) as well as by the expression of chemokine receptors and the production of corresponding ligands in the decidua, including CCR5/CCL4 (Kallikourdis et al 2007) and CCR4/CCL17 (Mjosberg et al 2010).…”

Section: Cells Of the Adaptive Immune System T Cells In The Deciduamentioning

confidence: 99%

“…The recruitment of decidual T cells is governed by human chorionic gonadotropin (Schumacher et al 2009) as well as by the expression of chemokine receptors and the production of corresponding ligands in the decidua, including CCR5/CCL4 (Kallikourdis et al 2007) and CCR4/CCL17 (Mjosberg et al 2010). In addition, Treg cells may proliferate (Mjosberg et al 2010) and mature (Dimova et al 2011) locally. An intriguing mechanism for regulating T cell traffic was recently shown; stroma cells in the decidua downregulated, by epigenetic mechanisms, their expression of chemokines CXCL9-11, known to recruit Th1 cells (Nancy et al 2012).…”

Section: Cells Of the Adaptive Immune System T Cells In The Deciduamentioning

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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“…In humans, CD4 + CD25 high Treg cells are enriched in the decidua, express markers of activation (CD45R0 and HLA-DR) and show a suppressive phenotype, with high expression of Foxp3 and CTLA-4 (Heikkinen et al, 2004;Tilburgs et al, 2006;Tilburgs et al, 2008;Mjosberg et al, 2010;Dimova et al, 2011). In contrast to mouse pregnancy, little is known about the specificity and the mechanisms that promote expansion of Treg cells in humans.…”

Section: Treg Cellsmentioning

confidence: 96%

Immune regulation at the fetal‐maternal interface with focus on decidual macrophages

Svensson‐Arvelund¹

2015

Linköping University Medical Dissertations

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A successful pregnancy requires that the maternal immune system adapts to tolerate the semi-allogeneic fetal-placental unit. This adaptation mainly occurs locally, i.e. at the fetal-maternal interface, where fetal-derived tissues come into close contact with maternal cells in the uterine endometrium (called decidua during pregnancy). decidual macrophages preferentially secreted the monocyte-and Treg cell-associated chemokines CCL2 and CCL18, while Th1-, Th2-and Th17-related chemokines were produced at low levels. These results suggest that decidual macrophages contribute to create the unique decidual cell composition and a tolerogenic immune environment that is compatible with fetal development. Further, by comparing decidual macrophages with different in vitro macrophage subsets, we showed that M-CSF and

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Maternal Foxp3 Expressing CD4⁺ CD25⁺ and CD4⁺ CD25⁻ Regulatory T‐Cell Populations are Enriched in Human Early Normal Pregnancy Decidua: A Phenotypic Study of Paired Decidual and Peripheral Blood Samples

Cited by 81 publications

References 48 publications

Granulocytic Myeloid-Derived Suppressor Cells Accumulate in Human Placenta and Polarize toward a Th2 Phenotype

Granulocytic Myeloid-Derived Suppressor Cells Accumulate in Human Placenta and Polarize toward a Th2 Phenotype

The Placenta in Toxicology. Part II

Immune regulation at the fetal‐maternal interface with focus on decidual macrophages

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