Role of Caspases in the Cytotoxicity of NK-92 Cells in Various Models of Coculturing with Trophoblasts

Milyutina, Yu. P.; Михайлова, В. А.; Pyatygina, K M; Demidova, E S; Malygina, Daria A.; Тертычная, Т.Е.; Arutjunyan, А. V.; Соколов, Д. И.; Selkov, S. A.

doi:10.1134/s0006297919100079

Cited by 3 publications

(1 citation statement)

References 59 publications

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“…On the other hand, the invasion of trophoblasts into the endometrium is accompanied by their influence on cells of the microenvironment, including endometrial, endothelial, and maternal NK cells [ 94 , 95 , 96 , 97 ]. Despite this, NK cells actively control the proliferation and migration of trophoblasts under conditions of physiological pregnancy, which in turn restrains the excessive cytotoxicity of NK cells [ 98 , 99 , 100 , 101 ]. Despite the lack of data on the effect on the trophoblast phenotype, NK-92 cell MVs reduce the proliferation but increase the migration of JEG-3 cells with no changes to their viability.…”

Section: Discussionmentioning

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: Discussionmentioning

confidence: 99%

Natural Killer Cell Derived Microvesicles Affect the Function of Trophoblast Cells

et al. 2023

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Caspase Activation in Trophoblast Cells after Interacting with Microparticles Produced by Natural Killer Cells in vitro

Milyutina

Korenevskii

Vasilyeva

et al. 2022

J Evol Biochem Phys

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Application of a JEG-3 organoid model to study HLA-G function in the trophoblast

et al. 2023

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The human placenta is a unique temporary organ with a mysterious immune tolerance. The formation of trophoblast organoids has advanced the study of placental development. HLA-G is uniquely expressed in the extravillous trophoblast (EVT) and has been linked to placental disorders. With older experimental methodologies, the role of HLA-G in trophoblast function beyond immunomodulation is still contested, as is its role during trophoblast differentiation. Organoid models incorporating CRISPR/Cas9 technology were used to examine the role of HLA-G in trophoblast function and differentiation. JEG-3 trophoblast organoids (JEG-3-ORGs) were established that highly expressed trophoblast representative markers and had the capacity to differentiate into EVT. CRISPR/Cas9 based on HLA-G knockout (KO) significantly altered the trophoblast immunomodulatory effect on the cytotoxicity of natural killer cells, as well as the trophoblast regulatory effect on HUVEC angiogenesis, but had no effect on the proliferation and invasion of JEG-3 cells and the formation of TB-ORGs. RNA-sequencing analysis further demonstrated that JEG-3 KO cells followed similar biological pathways as their wild-type counterparts during the formation of TB-ORGs. In addition, neither HLA-G KO nor the exogenous addition of HLA-G protein during EVT differentiation from JEG-3-ORGs altered the temporal expression of the known EVT marker genes. Based on the JEG-3 KO (disruption of exons 2 and 3) cell line and the TB-ORGs model, it was determined that HLA-G has a negligible effect on trophoblast invasion and differentiation. Despite this, JEG-3-ORG remains a valuable model for studying trophoblast differentiation.

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Role of Caspases in the Cytotoxicity of NK-92 Cells in Various Models of Coculturing with Trophoblasts

Cited by 3 publications

References 59 publications

Natural Killer Cell Derived Microvesicles Affect the Function of Trophoblast Cells

Natural Killer Cell Derived Microvesicles Affect the Function of Trophoblast Cells

Caspase Activation in Trophoblast Cells after Interacting with Microparticles Produced by Natural Killer Cells in vitro

Application of a JEG-3 organoid model to study HLA-G function in the trophoblast

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