CD25+FOXP3+ and CD4+CD25+ cells distribution in decidual departments of women with severe and mild pre‐eclampsia: Comparison with healthy pregnancies

Vlaho, Martina Orlović; Tomić, Vajdana; Vukojević, Katarina; Vasilj, Anja; Pejic, Renato; Lesko, Josip; Šoljić, Violeta

doi:10.1111/aji.13281

Cited by 5 publications

(3 citation statements)

References 43 publications

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“…FOXP3 mRNA expression in CD8 + T cells was upregulated in our study, which was surprising as the results of numerous recent studies emphasize the role of regulatory CD4 + CD25 + FOXP3 + T cells for fetal acceptance [41][42][43][44][45][46]. The CD8 + FOXP3 + Treg subtype accounts for a small percentage of Treg cells and is much less studied compared to CD4 + FOXP3 + subpopulation.…”

Section: Discussioncontrasting

confidence: 80%

Decreased Expression of Cytotoxic Proteins in Decidual CD8+ T Cells in Preeclampsia

Šoljić

Barbarić

Vukoja

et al. 2021

Biology

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In our study, we aimed to establish expression of cytotoxic CD8+ T cells in the decidua basalis and the maternal peripheral blood (mPBL) of severe and mild preeclampsia (PE) and compare to healthy pregnancies. Decidual tissue and mPBL of 10 women with mild PE, 10 women with severe PE, and 20 age-matched healthy pregnancy controls were analyzed by double immunofluorescence and qPCR, respectively. By double immunofluorescence staining, we found a decreased total number of cells/mm2 in decidua basalis of granulysin (GNLY)+ (p ˂ 0.0001), granzyme B (GzB)+(p ˂ 0.0001), GzB+CD8+(p ˂ 0.0001), perforin (PRF1)+ (p ˂ 0.0001), and PRF1+CD8+ (p ˂ 0.01) in the severe PE compared to control group. Additionally, we noticed the trend of lower mRNA expression for GNLY, granzyme A (GZMA), GzB, and PRF1 in CD8+ T cells of mPBL in mild and severe PE, with the latter marker statistically decreased in severe PE (p ˂ 0.001). Forkhead box P3 (FOXP3) mRNA in CD8+ T cells mPBL was increased in mild PE (p ˂ 0.001) compared to controls. In conclusion, severe PE is characterized by altered expression of cytotoxic CD8+ T cells in decidua and mPBL, suggesting their role in pathophysiology of PE and fetal-maternal immune tolerance.

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Section: Discussioncontrasting

confidence: 80%

Decreased Expression of Cytotoxic Proteins in Decidual CD8+ T Cells in Preeclampsia

Šoljić

Barbarić

Vukoja

et al. 2021

Biology

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“…36,37 In humans, Treg cells are increased in the peripheral blood and decidua during pregnancy. 38,39 Though the alternation of decidual Treg cells in women with preeclampsia has been widely debated, [40][41][42][43][44][45][46] there is consensus on the functional or qualitative changes of Treg cells. 42,43,46 A report analyzing the T cell receptor repertoire of the effector Treg cells, which have particularly strong immunosuppressive activity, revealed that the decidual Treg cells had more clonally expanded TCR clonotypes than the peripheral blood in human pregnancies 46 ; this suggests that decidual Treg cells clonally increased in response to specific antigens in the fetomaternal interface.…”

Section: Maintenance Of An Allogeneic Pregnancy From Immunological As...mentioning

confidence: 99%

Immunological regulation and the role of autophagy in preeclampsia

Nakashima,

Furuta,

Yoshida‐Kawaguchi

et al. 2024

American J Rep Immunol

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Autophagy is a bulk degradation system that maintains cellular homeostasis by producing energy and/or recycling excess proteins. During early placentation, extravillous trophoblasts invade the decidua and uterine myometrium, facing maternal immune cells, which participate in the immune suppression of paternal and fetal antigens. Regulatory T cells will likely increase in response to a specific antigen before and during early pregnancy. Insufficient expansion of antigen‐specific Treg cells, which possess the same T cell receptor, is associated with the pathophysiology of preeclampsia, suggesting sterile systemic inflammation. Autophagy is involved in reducing inflammation through the degradation of inflammasomes and in the differentiation and function of regulatory T cells. Autophagy dysregulation induces protein aggregation in trophoblasts, resulting in placental dysfunction. In this review, we discuss the role of regulatory T cells in normal pregnancies. In addition, we discuss the association between autophagy and regulatory T cells in the development of preeclampsia based on reports on the role of autophagy in autoimmune diseases.

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“…Tregs suppress other immune system cells through cell-cell interactions by receptors, including CTLA-4, PD-1, LAG-3, and Tim-3, and by the production of such cytokines as Il-10, IL-6, TGFβ, and Il-35 [2,3]. Dysfunction in Tregs has been extensively studied not only in cases of preterm birth and miscarriage [4,5], but also in cases of preeclampsia [6,7].…”

Section: Introductionmentioning

confidence: 99%

FOXP3-positive cell infiltration in the chorionic villi is increased in the placenta accreta and decreased in the placental abruption

Dutsch-Wicherek,

Nowakowski,

Faryna

et al. 2023

Ginekol Pol

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Objectives: Growing data suggest a role of Treg cells in placentation. The aim of the study was to evaluate Treg cells (FOXP3-positive cells) placental bed infiltration in patients with placenta accrete syndrome (PAS) and patients who experienced placental abruption. Material and methods:The study group included 13 patients with PAS and the control group consisted of 66 women who had caesarean (CD) delivery of whom, 44 patients with elective caesarean (EC) delivery, and 22 patients with urgent caesarean (UC) delivery due to placental abruption. FOXP3 cell infiltration was assessed by means of immunohistochemistry in placental chorionic villous (CV) and in the decidua (D) and cumulatively in the placental bed (PB). Results:We observed significant difference in the degree of FOXP3-positive cell CV infiltration between studied groups (p = 0.04). FOXP3-positive cells were the most commonly observed in PAS patients, while, they were the least frequently presented in patients after UC. The immunoreactivity for FOXP3-positive cells in CV were as follows: PAS 5 (38%), urgent CS 1 (5%) and elective CS 8 (18%) subjects. We found no difference in the presence of FOXP3-positive cells in the D (p = = 0.35) and in the PB (p = 0.23) of analyzed groups. FOXP3-cell infiltration was not related with patient age, BMI, gestational age and neonatal birth weight. Conclusions:Our study provides further evidence that abnormal invasive placentation is an associated disturbance of the maternal immune response. Accordingly, we have theorized that alteration of the FOXP3-positive Treg cell infiltration into the placental bed allows trophoblast cell invasion.

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CD25⁺FOXP3⁺ and CD4⁺CD25⁺ cells distribution in decidual departments of women with severe and mild pre‐eclampsia: Comparison with healthy pregnancies

Cited by 5 publications

References 43 publications

Decreased Expression of Cytotoxic Proteins in Decidual CD8+ T Cells in Preeclampsia

Decreased Expression of Cytotoxic Proteins in Decidual CD8+ T Cells in Preeclampsia

Immunological regulation and the role of autophagy in preeclampsia

FOXP3-positive cell infiltration in the chorionic villi is increased in the placenta accreta and decreased in the placental abruption

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