Characteristics of Natural Killer Cell Interaction with Trophoblast Cells During Pregnancy

Bazhenov, D O; Khokhlova, Evgeniya V.; Viazmina, Larisa; Furaeva, K. N.; Михайлова, В. А.; Kostin, Nikolay Anatolievich; Selkov, S. A.

doi:10.2174/1566524019666190808103227

Cited by 9 publications

(7 citation statements)

References 97 publications

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“…After that, JEG-3 cells were treated with monoclonal antibodies against CD45, CD54, CD56, CD105, CD126, CD130, CD181, CD119 (BD, USA), and CD120a (R&D Systems, Minneapolis, MN, USA), and cells treated with isotype antibodies as controls, in accordance with the manufacturer’s instructions. The choice of antibodies was based on our own data and data from the literature on the change in JEG-3 phenotype in the presence of cytokines [ 63 , 66 ] as well as the phenotyping of NK-92 cells and their microvesicles ( Table 1 ) [ 60 , 67 ]. Fluorescence was analyzed using a FACS Canto II flow cytometer (Becton Dickinson, Franklin Lakes, NJ, USA).…”

Section: Methodsmentioning

confidence: 99%

Natural Killer Cell Derived Microvesicles Affect the Function of Trophoblast Cells

et al. 2023

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The interaction of natural killer (NK) and trophoblast cells underlies the formation of immune tolerance in the mother–fetus system and the maintenance of the physiological course of pregnancy. In addition, NK cells affect the function of trophoblast cells, interacting with them via the receptor apparatus and through the production of cytokines. Microvesicles (MVs) derived from NK cells are able to change the function of target cells. However, in the overall pattern of interactions between NK cells and trophoblasts, the possibility that both can transmit signals to each other via MVs has not been taken into account. Therefore, the aim of this study was to assess the effect of NK cell-derived MVs on the phenotype, proliferation, and migration of trophoblast cells and their expression of intracellular messengers. We carried out assays for the detection of content transferred from MV to trophoblasts. We found that NK cell-derived MVs did not affect the expression of CD54, CD105, CD126, CD130, CD181, CD119, and CD120a receptors in trophoblast cells or lead to the appearance of CD45 and CD56 receptors in the trophoblast membrane. Further, the MVs reduced the proliferation but increased the migration of trophoblasts with no changes to their viability. Incubation of trophoblast cells in the presence of MVs resulted in the activation of STAT3 via pSTAT3(Ser727) but not via pSTAT3(Tyr705). The treatment of trophoblasts with MVs did not result in the phosphorylation of STAT1 and ERK1/2. The obtained data indicate that NK cell-derived MVs influence the function of trophoblast cells, which is accompanied by the activation of STAT3 signaling.

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Section: Methodsmentioning

confidence: 99%

Natural Killer Cell Derived Microvesicles Affect the Function of Trophoblast Cells

et al. 2023

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“…NK-92 cells were pre-cultured in a 24-well plate in the presence of TNFα (50 IU/mL), IL-10 (10 IU/mL), IFNγ (1000 IU/mL) or TGFβ (5 ng/mL) for 24 h or 96 h. The incubation with the cytokines was carried out for 24 h, since it was previously established that the incubation of NK-92 cells with the supernatants of placenta samples led to a change in the expression of surface cell receptors [59]. The incubation time of 96 h was chosen to match the conditions of the experiments for the co-cultivation of NK-92 cells and JEG-3 cells.…”

Section: Evaluation Of the Cytotoxicity Of The Nk-92 Cell Line After ...mentioning

confidence: 99%

Pro- and Anti-Inflammatory Cytokines in the Context of NK Cell–Trophoblast Interactions

Михайлова

Grebenkina

Khokhlova

et al. 2022

IJMS

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During pregnancy, uterine NK cells interact with trophoblast cells. In addition to contact interactions, uterine NK cells are influenced by cytokines, which are secreted by the cells of the decidua microenvironment. Cytokines can affect the phenotypic characteristics of NK cells and change their functional activity. An imbalance of pro- and anti-inflammatory signals can lead to the development of reproductive pathology. The aim of this study was to assess the effects of cytokines on NK cells in the presence of trophoblast cells in an in vitro model. We used TNFα, IFNγ, TGFβ and IL-10; the NK-92 cell line; and peripheral blood NK cells (pNKs) from healthy, non-pregnant women. For trophoblast cells, the JEG-3 cell line was used. In the monoculture of NK-92 cells, TNFα caused a decrease in CD56 expression. In the coculture of NK cells with JEG-3 cells, TNFα increased the expression of NKG2C and NKG2A by NK-92 cells. Under the influence of TGFβ, the expression of CD56 increased and the expression of NKp30 decreased in the monoculture. After the preliminary cultivation of NK-92 cells in the presence of TGFβ, their cytotoxicity increased. In the case of adding TGFβ to the PBMC culture, as well as coculturing PBMCs and JEG-3 cells, the expression of CD56 and NKp44 by pNK cells was reduced. The differences in the effects of TGFβ in the model using NK-92 cells and pNK cells may be associated with the possible influence of monocytes or other lymphoid cells from the mononuclear fraction.

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“…Preeclampsia and many other pathophysiological and physiological processes in the placenta are intimately linked to changes in the activity and phenotypes of immune cells, including natural killer (NK) cells and macrophages, which are the most common decidual leukocytes [78]. Both NK cells and macrophages show phenotypic changes over the course of pregnancy [78,79]. Both of these immune cell types are regulated by melatonin as well as melatonin-induced BMAL1 and alpha 7 nicotinic acetylcholine receptor (α7nAChR), with autocrine melatonin acting to switch macrophages from an M1-like pro-inflammatory phenotype to an M2-like phenotype [80].…”

Section: Placenta and Immune Cellsmentioning

confidence: 99%

The Role of Prenatal Melatonin in the Regulation of Childhood Obesity

Ivanov

Evsyukova

Mazzoccoli

et al. 2020

Biology

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There is a growing awareness that pregnancy can set the foundations for an array of diverse medical conditions in the offspring, including obesity. A wide assortment of factors, including genetic, epigenetic, lifestyle, and diet can influence foetal outcomes. This article reviews the role of melatonin in the prenatal modulation of offspring obesity. A growing number of studies show that many prenatal risk factors for poor foetal metabolic outcomes, including gestational diabetes and night-shift work, are associated with a decrease in pineal gland-derived melatonin and associated alterations in the circadian rhythm. An important aspect of circadian melatonin’s effects is mediated via the circadian gene, BMAL1, including in the regulation of mitochondrial metabolism and the mitochondrial melatoninergic pathway. Alterations in the regulation of mitochondrial metabolic shifts between glycolysis and oxidative phosphorylation in immune and glia cells seem crucial to a host of human medical conditions, including in the development of obesity and the association of obesity with the risk of other medical conditions. The gut microbiome is another important hub in the pathoetiology and pathophysiology of many medical conditions, with negative consequences mediated by a decrease in the short-chain fatty acid, butyrate. The effects of butyrate are partly mediated via an increase in the melatoninergic pathway, indicating interactions of the gut microbiome with melatonin. Some of the effects of melatonin seem mediated via the alpha 7 nicotinic receptor, whilst both melatonin and butyrate may regulate obesity through the opioidergic system. Oxytocin, a recently recognized inhibitor of obesity, may also be acting via the opioidergic system. The early developmental regulation of these processes and factors by melatonin are crucial to the development of obesity and many diverse comorbidities.

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Characteristics of Natural Killer Cell Interaction with Trophoblast Cells During Pregnancy

Cited by 9 publications

References 97 publications

Natural Killer Cell Derived Microvesicles Affect the Function of Trophoblast Cells

Natural Killer Cell Derived Microvesicles Affect the Function of Trophoblast Cells

Pro- and Anti-Inflammatory Cytokines in the Context of NK Cell–Trophoblast Interactions

The Role of Prenatal Melatonin in the Regulation of Childhood Obesity

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