Dmitriy I Sokolov

D. O. Ott Research Institute of Obstetrics and Gynecology · Immunology and Intercellular interaction

Extracellular vesicles that are shed from the plasma membrane contain a wide range of molecules, among which are proteins, lipids, nucleic acids, and sugars. The cytotoxic proteins of natural killer cells play a key role in the implementation of their cytolytic functions. One of the important steps in understanding the distant communication of cell...

NK cell development is affected by their cellular microenvironment and cytokines, including IL-15 and IL-18. NK cells can differentiate in secondary lymphoid organs, liver and within the uterus in close contact with trophoblast cells. The aim was to evaluate changes in the NK cell phenotype and function in the presence of IL-15, IL-18 and JEG-3, a...

Microvesicles (MVs) are plasma extracellular vesicles ranging from 100 (150) to 1000 nm in diameter. These are generally produced by different cells through their vital activity and are a source of various protein and non-protein molecules. It is assumed that MVs can mediate intercellular communication and modulate cell functions. The interaction b...

The interaction of natural killer and trophoblast cells underlies maternal-fetal immune tolerance. The data on the participation of endoglin (ENG, CD105), or its soluble form, in the regulation of the communication of these cells are currently insufficient. In this study, we have investigated the role of endoglin in the intercellular interactions b...

Communication between natural killer cells (NK cells) and monocytes/macrophages may play an important role in immunomodulation and regulation of inflammatory processes. The aim of this research was to investigate the impact of NK cell-derived large extracellular vesicles on monocyte function because this field is understudied. We studied how NK-cel...

Natural killer (NK) cells are a population of innate immune cells that have cytotoxic functions and are involved in protecting the body from viruses and transformed cells. Placental development is determined largely by the interaction of decidual NK cells and trophoblast cells. During pregnancy, NK cells accumulate around trophoblast cells, while r...

BACKGROUND: Endothelial dysfunction is the leading pathogenetic factor of preeclampsia. The function of the endothelium may be reflected in its ability to form microvesicles, which are generated by cells through the regulated shedding of the plasma membrane. AIM: The aim of this study was to evaluate the endothelial microvesicles count in periphera...

Natural killer cells (NK cells) are a population of innate immune lymphocytes capable of cytolysis of infected or transformed cells without prior sensitization. Natural killers are detected in various organs and tissues and may differ in phenotypic and functional characteristics depending on localization. For example, NK cells are the dominant popu...

Natural killer (NK) cells are a population of innate immune cells that have cytotoxic functions and are involved in protecting the body from viruses and transformed cells. Placental development is largely determined by the interaction of decidual NK cells and trophoblast cells. During pregnancy, NK cells accumulate around trophoblast cells, while r...

Natural killer cells (NK cells) exert cytotoxicity towards target cells in several ways, including the expression of apoptosis-mediating ligands (TRAIL, FasL). In addition, NK cells themselves may be susceptible to apoptosis due to the expression of TRAIL receptors. These receptors include TRAIL-R1 (DR4), TRAIL-R2 (DR5), capable of inducing apoptos...

This review presents current data on the origin of monocytes/macrophages, the conditions necessary for the differentiation of monocytes into M1 or M2 macrophages. Three subpopulations of peripheral blood monocytes are described: (I) classical – the main subpopulation (85-90%), effectively carrying out phagocytosis; (II) intermediate monocytes (5-10...

BACKGROUND: Alteration in the composition and function of endometrial immune cells, in particular NK cells, are associated with implantation and placentation pathology, which is considered as one of the causes of reproductive losses. However, data regarding abnormalities in the number and activity of NK cells in repeated implantation failures, incl...

BACKGROUND:In obstetrics and reproductive medicine, the use of intravenous immunoglobulin remains controversial. There are no clearly developed indications for immunoglobulins therapy. The search for immunological criteria for prescribing this therapy is an urgent task AIM:The aim of this study was to evaluate the effectiveness of the use of intrav...

Extracellular vesicles (EV) are currently considered potential biomarkers of diseases, as well as “biological constructs” for targeted drug delivery. Extracellular vesicles represent a heterogeneous population of membrane vesicles formed by various cell populations, including immune cells. At present time, EV are divided into exosomes, microvesicle...

Natural killer (NK) cells represent one of the innate lymphoid cell subsets, which are often studied in the context of antitumor and antiviral immunity, as well as due to their localization in the zone of the mother-fetus contact (in the uterus), therefore underlying their extensive investigation in developing pregnancy. At the same time, their rol...

Each stage of angiogenesis depends on the nature of the communication between endothelial cells and the microenvironment, and on the complex balance between stimulators and inhibitors of this process. Natural killer cells secrete a variety of cytokines and chemokines that can influence the microenvironment. The aim of this study was to assess the e...

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. Mi...

Angiogenesis is the development of new blood vessels from pre-existing ones. It is a complex multifaceted process that is essential for the adequate functioning of human organisms. The investigation of angiogenesis is conducted using various methods. One of the most popular and most serviceable of these methods in vitro is the short-term culture of...

Intercellular communication plays a huge role in the vital activity of living organisms. At present, far less studied is distant cellular communication, in which, along with autocrine and paracrine regulations by soluble factors (e.g. cytokines and growth factors), of particular interest is communication by means of microparticles via their ligand-...

Natural killer cells (NK cells) represent a group of lymphocytes of innate immunity. In addition to NK cells of peripheral blood, tissue-resident populations are described. NK cells of the decidual envelope (decidual NK cells) represent one of the local NK cell populations. Decidual NK cells differ in phenotype and function from peripheral blood NK...

Microvesicles are membrane-derived formations ranging in size from 100 to 1000 nm, being produced by a variety of resting and activated cells. They can transfer their cargo to target cells, regulate physiological processes, and participate in the development of clinical disorders. Among the microvesicles of different origin, natural killers are of...

Иммуноглобулины для внутривенного введения (ВВИГ) применяют в терапии бесплодия. Предполагается влияние ВВИГ на цитотоксическую функцию NK-клеток, однако механизм действия ВВИГ остается неясным. Цель: Оценка влияния препарата ВВИГ на цитотоксичность NK-клеток в отношении клеток-мишеней линии К-562 и клеток трофобласта линии JEG-3. Материалы и метод...

Endometriosis is a chronic gynecological disease, which poses a serious problem in terms of diagnosis and treatment. Despite decades of research, there are no specific signs and symptoms and no blood tests to clinically confirm the diagnosis, which makes timely diagnosis and treatment difficult. Therefore, the search for new markers for early non-i...

We analyzed the effect of individual cytokines that are secretory products of placenta typical of the uteroplacental bed. The proinflammatory cytokines IL-6, IFNγ, and IL-1β increased the expression of TGFβR2 molecule by trophoblast cells, while VEGF and PLGF increased the expression of CD45, CD29, and CD54 adhesion molecule by trophoblast cells. T...

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-in...

Natural killer cells (NK cells) are innate immunity lymphocytes. NK cell differentiation is controlled by the cellular microenvironment and locally produced cytokines, including IL-2, IL-15 and IL-18. NK cells are present in various tissues, forming pools of tissue-resident NK cells, e.g., decidual NK cell pool. Peripheral blood NK cells (pNK cells...

Natural killer cells (NK) are innate immune lymphocytes produced in the bone marrow. Isolation of NK cells as a separate population of lymphocytes is related to discovery of their ability to induce the death of tumor cells without prior sensitization. In this review, an attempt was made to systematize the numerous data on the biology of NK cells pr...

T-lymphocytes are present in the endometrium before pregnancy and their number varies depending on menstrual cycle stage. Despite T-lymphocyte population heterogeneity, there is no clear vision of general mechanisms of decidua T-lymphocyte pool formation. One of the assumed variants is T-lymphocyte proliferation in situ. The study objective is to e...

Many infertile couples cannot achieve pregnancy after repeatedly implemented assisted reproductive technology (ART) programs, as well as its successful prolongation, even with the transfer of good-quality euploid embryos. In this connection, repeated implantation failures (RIFs) in the in vitro fertilization (IVF) protocols and recurrent miscarriag...

Monocytes\macrophages regulate angiogenesis via cytokine production and contact interactions with endothelial cells (ECs). The biological effects of macrophage-derived microvesicles (MVs) are studied using cell lines, such as monocytic leukemia THP-1 cell line. The effect of MVs produced by THP-1 cells on EC phenotype and functions remain understud...

Extracellular vesicles that are shed from the plasma membranes take an active part in intercellular communication, transporting a wide range of molecules, including proteins, lipids, nucleic acids and carbohydrates, being of great functional importance. One of the steps to better understanding of distant communications of cells and their regulatory...

Glaucoma is one of the leading causes of irreversible blindness worldwide, being an age-related disease. Its pathogenesis still is not fully understood. A particular interest is attracted to evaluation of the cytokine concentrations in the trabecular meshwork cell culture, and in the aqueous humor (AH) taken from the same patient, since such data m...

Objective The present study was to estimate the role of cytokines for trophoblast death in NK cells presence. Methods This study involves assessment of NK-92 line NK cell cytotoxic activity against JEG-3 line cells, in presence of cytokines. We also assessed the effect of secretory placenta products on NK cell cytotoxic activity toward JEG-3 line...

Glaucoma is one of the leading causes of irreversible blindness worldwide and belongs to age-related diseases. However, its pathogenesis is not fully understood. Primary open-angle glaucoma (POAG), pseudoexfoliative (PE) glaucoma are the most common forms of glaucoma. Increased intraocular pressure (IOP) is one of the main risk factors for glaucoma...

We studied the effect of microvesicles derived from cells of the NK-92 cell line on the for-mation of tube-like structures by endothelial cells of the ЕА.Hy926 cell line. Microvesicles were isolated by differential centrifugation and their size was controlled by granulometric analysis using dynamic light scattering method. The effect of microvesicl...

Morphological properties and the size of microvesicles were assessed using atomic force microscopy, electron microscopy, and granulometric analysis. As these methods require significant numbers of microvesicles, we chose microvesicles derived from cell lines for our research.

Microvesicles (MVs) are small (100-1000 nm) subcellular structures produced by both motionless and activated cells that can transfer molecules to target cells, and regulate physiological and pathological processes. MVs of leukocyte origin, in particular those produced by natural killer cells (NK cells), remain the least studied population of MVs. N...

Development of angiogenesis depends on the functional state of endothelial cells, as well as on the balanced secretion of cytokines, growth factors and chemokines by endothelial cells and cells of microenvironment. Macrophages represent an essential component of the microenvironment and take part in the formation of blood vessels both due to the pr...

Background Maternal natural killer cells (NK cells) are a prevailing leukocyte population in the uteroplacental bed. The contact interaction and/or cytokine production of these cells controls trophoblast differentiation, migration and invasion. Objective To assess the impact of supernatants obtained during culturing of placentas from the first and...

Natural killer (NK) cells are the main population of leukocytes in decidua during the first trimester of pregnancy. NK cells can have contact with trophoblast cells during pregnancy, which raises the possibility of mutual influence. This research aimed to evaluate the proliferation and phenotype of peripheral blood NK cells in the presence of troph...

The endothelium of blood vessels plays an important role in the regulation of normal and pathological processes occurring in the tissues. Monoclonal antibodies (MAbs) to endoglin (CD105), a marker of endothelial cells, are considered as potential agents to affect the functional characteristics of endothelial cells. Here, we report the ability of MA...

Natural killer (NK) cells are of special interest among a multitude of microvesicle (MV) source cells. NK cells are a lymphocyte subpopulation performing contact cytolysis of virus-infected cells and tumor cells. Each of the NK cell populations has a unique receptor repertoire on its surface and, thus, unique functions. During their contact with a...

Studies of interactions between natural killer (NK) cells and trophoblasts and identification of conditions for the NK cells to perform their cytotoxic function are of fundamental and practical importance for understanding their role in the development of pathological processes and complications during pregnancy. In this study, we examined changes...

The aim of this research was to assess the proliferative activity of Natural Killer Cells (NK cells) from Peripheral Blood Mononuclear Cells (PBMCs) in the presence of trophoblast cells in women with a history of recurrent miscarriages. We examined the peripheral blood of women with recurrent miscarriage in the proliferative (n = 12) or secretory (...

The trial objective was to determine the peripheral blood NK cells cytotoxic activity effect on trophoblast cells at recurrent pregnancy loss (RPL). The investigation involved non-pregnant women with PRL in proliferating and secretory menstrual cycle phases (PMCPh and SMCPh, respectively); women of 6–7 weeks pregnancy with RPL in past medical histo...

Preeclampsia still remains one of the most severe pregnancy complications and is an actual problem in the obstetrics practice. At present, the joint impact of cytokines and other placenta secreted factors on trophoblast cell functional activity during preeclampsia complicated pregnancy remains unclear. The aim of the study is to estimate the surfac...

Regulation of angiogenesis in the utero-placental bed determines adequate trophoblast invasion, placenta formation and development, as well as successful course of pregnancy. Natural killer (NK) cells, macrophages and trophoblast have the most significant effect on angiogenesis. To date, the functions of cells participating in placenta formation ha...

Angiogenesis is a process of new blood vessel formation, which plays a significant role in carcinogenesis and the development of diseases associated with pathological neovascularization. An important role in the regulation of angiogenesis belongs to several key pathways such as VEGF-pathways, TGF-β-pathways, and some others. Introduction of small i...

We studied changes in angiogenesis during contact interaction of natural killer cells and endothelial cells in the presence of secretory products of trophoblast cells activated by various cytokines. Activated trophoblast regulates angiogenesis by producing soluble factors that affect endothelial cells either directly or indirectly through activatio...

Hypothesis/aims of study. Endometriosis is the main cause of infertility and social maladjustment in women, caused by the presence of inflammatory endometriotic implants outside the uterus. A number of chemokines, including interferons, compromise the immune response on the development of endometriosis raising the interest to the investigation of i...

We evaluated cytotoxic activity of peripheral blood NK cells towards trophoblast cells. NK cells either isolated or in the composition of mononuclear cell fraction, caused death of trophoblast cells. In women with physiological pregnancy, the cytotoxic effect of NK cells present in mononuclear cell fraction preincubated with IL-2 was lower than in...

All lymphoid cells are referred to as an innate or adaptive immunity unit in terms of the mechanisms of performing immune reactions. The functional activity of natural killer (NK) cells is not associated with pre-activation processes resulting from contact with antigen, rearrangement of antigen-recognition receptor genes, and clonal proliferation....

Microvesicles are a new field of biological research. They are subcellular structures ranging in size from 100 to 1000 nm and found in practically all human biological fluids. Their sources are different cells. Microvesicles have a diverse internal composition and carry a wide spectrum of mol-ecules on their surface, which determines their particip...

Microvesicles are a new field of biological research. They are subcellular structures ranging in size from 100 to 1000 nm and found in practically all human biological fluids. Their sources are different cells. Microvesicles have a diverse internal composition and carry a wide spectrum of molecules on their surface, which determines their participa...

At the present time, a broad spectrum of CD8+ T lymphocyte subsets is revealed, including naïve cells, memory cells and regulatory subpopulations. Along with cells with high cytolytic activity, some subsets with marked regulatory activity were found there. Each subpopulation is characterized by a set of produced mediators, surface and intracellular...

Soluble endoglin (sEng) is a fragment of a membrane-associated receptor (CD105) expressed on endothelial cells, mesenchymal stem cells and trophoblast cells. It is considered as a regulatory factor involved in the development of preeclampsia (PE) and cancer-associated neo-angiogenesis. The purpose of this study was to describe a new sandwich ELISA...