Estriol in formation of mononuclear cells tolerogenic features.

Estriol (E) is one of hormones whose synthesis is mainly associated with pregnancy. The hormone can also regulate immune cells functions. E influence on monocyte indoleamine-2,3-dioxygenase (IDO1) activity and Treg and NK cells' markers expression was investigated.

Estriol and commensal microflora strains regulate innate lymphoid cells functional activity in multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune neurodegenerative disease in which the immune system attacks myelin basic protein of nerve axons. Recently, there has been growing interest in studying the role of a newly described population of immunity cells - innate lymphoid cells (ILCs) in the pathogenesis of the disease. At the same time, it was found that during pregnancy there is a weakening of Th1-mediated autoimmune pathologies manifestations, including MS.

Leptin regulates thymic plasmacytoid dendritic cell ability to influence the thymocyte distribution in vitro.

Leptin, the adipocyte-derived hormone, involved in regulating food intake and body weight, plays an important role in immunity and reproduction. Leptin signals via the specific membrane receptors expressed in most types of immune cells including dendritic cells (DCs) and thymocytes. Leptin enhances thymopoiesis and modulates T-cell-mediated immunity.

The effect of kisspeptin on the functional activity of peripheral blood monocytes and neutrophils in the context of physiological pregnancy.

Hypothalamic hormone kisspeptin is also produced by placental syncytiotrophoblast. Blood leukocytes express a specific membrane receptor of kisspeptin (KISS-1R). Since kisspeptin-54 enters the bloodstream during pregnancy, the hormone has a systemic effect on the leukocytes only in this period.

Role of Kisspeptin in Regulation of Reproductive and Immune Reactions.

The work is focused on physiological role of the hormone kisspeptin produced by neurons of the hypothalamus anterior zone, which is a key regulator of reproduction processes. Role of the hormone in transmission of information on metabolic activity and induction of the secretion of gonadotropin-releasing hormone (GnRH) by the hypothalamus that determines gestation processes involving fertilization, placentation, fetal development, and child birth is considered. The literature data on molecular mechanisms and effects of kisspeptin on reproductive system including puberty initiation are summarized and analyzed.

Estriol in regulation of cell-mediated immune reactions in multiple sclerosis.

The effect of pregnancy hormone estriol (E) on innate and adaptive immunity cells functions in patients with multiple sclerosis (MS) in comparison with healthy donors (HD) was studied. E inhibited phagocytic activity of neutrophils and enhanced monocytes IDO activity. Treg percentage increased and number of Th17 and iNKT cells decreased under E influence.

Mechanisms of Antiphospholipid Syndrome Induction: Role of NKT Cells.

The review discusses the mechanisms of participation of natural killer T cells (NKT cells) in the induction of antiphospholipid antibodies (APA) that play a major pathogenetic role in the formation of antiphospholipid syndrome (APS), summarizes the data on APS pathogenesis, and presents modern concepts on the antibody formation involving follicular helper type II NK cells.

Effect of Estriol, Chorionic Gonadotropin, and Oncostatin M on the Expression of Recombinase RAG-1 in Regulatory T Lymphocyte Subpopulations.

We studied the effect of estriol, chorionic gonadotropin, oncostatin M, and hormone-cytokine combinations on the expression of recombinase RAG-1 in T-regulatory (Treg) and T helper 17 (Th17) lymphocytes. It was found that estriol in a concentration corresponding to the first trimester of pregnancy increased the level of Treg (CD4FoxP3) cells and suppressed the formation of Th17 (CD4RORC) lymphocytes. This effect was nor observed after individual administration of chorionic gonadotropin and oncostatin M, but some combinations of the studied hormones with oncostatin M increased the percentage of CD4FOXP3 cells.

Regulation of Recombinase Rag-1 Expression by Female Sex Steroids in Treg and Th17 Lymphocytes: Role of Oncostatin M.

The effect of estradiol (E), progesterone (P), and oncostatin M (OSM) on the differentiation of CD4 T cells to T regulatory (Treg) lymphocytes and T helpers 17 (Th17) was investigated. The possibility of revision of the T cell receptor in these subpopulations by evaluating the expression of RAG-1 recombinase was also studied. E at concentrations characteristic of pregnancy trimester I, but no P or OSM, increased the Treg level.

Mechanisms of Leptin and Ghrelin Action on Maturation and Functions of Dendritic Cells.

Molecular mechanisms of the immunomodulatory effects of leptin and ghrelin in concentrations typical for pregnancy on the maturation and functional activity of dendritic cells (DCs) generated from the peripheral blood monocytes of women are investigated. The presence of leptin during DC maturation did not affect the levels of CD83CD1c, CD86CD1c, and HLA-DRCD1c DCs, but increased the amount and the activity of the enzyme indoleamine 2,3-dioxygenase (IDO). Cell culturing in the presence of ghrelin or combination of leptin and ghrelin reduced the percentage of CD86CD1c DCs but did not affect the levels of CD83CD1c and HLA-DRCD1c DCs.

Hormonal Regulation of Dendritic Cell Differentiation in the Thymus.

We studied the effect of hormones estriol, ghrelin, kisspeptin, and chorionic gonadotropin in concentrations corresponding to their content in the peripheral blood in each trimester of pregnancy on the expression of membrane molecules on myeloid and plasmacytoid dendritic cells of the thymus. It was found that thymic myeloid dendritic cells are sensitive to the action of estriol and kisspeptin. Estriol in a concentration of the first trimester of pregnancy reduces the number of myeloid dendritic cells expressing receptor for thymic stromal lymphopoietin (CD11c+TSLP-R) and inhibitory molecule B7-H3 (CD11cCD276).

Role of PKA and PI3K in Leptin and Ghrelin Regulation of Adaptive Subpopulations of Regulatory CD4+ T-Lymphocyte Formation.

The role of phosphatidylinositol-3 kinase (PI3K) and protein kinase A (PKA) in leptin and ghrelin regulation of formation of adaptive (a) subpopulations of CD4+ T-lymphocytes (helper (h) cells producing interleukin-17A) (aTһ17) and of T-regulatory lymphocytes (aTreg) in the context of physiological pregnancy is established. It is shown that leptin at a concentration typical for the second half of pregnancy (trimesters II-III) enhances the differentiation of aTһ17 with a high level of interleukin-17A (IL-17A) production and the expression of the chemokine receptor CCR6 with the participation of PI3K. Simultaneously, leptin reduces formation of aTreg expressing the suppressor molecule CTLA-4, which determines the function of these cells.

Effect of bacterial components of mixed culture supernatants of planktonic and biofilm Pseudomonas aeruginosa with commensal Escherichia coli on the neutrophil response in vitro.

Pseudomonas aeruginosa (PA) responsible for acute and chronic infections often forms a well-organized bacterial population with different microbial species including commensal strains of Escherichia coli. Bacterial extracellular components of mixed culture can modulate the influence of bacteria on the neutrophil functions. The objective of this study was to compare the effect of pyocyanin, pyoverdine, LPS, exopolysaccharide of single species and mixed culture supernatants of PA strains and E.

MicroRNA in hormonal mechanisms of regulation of NK cell function.

We investigated the effect of human chorionic gonadotropin, estriol, leptin, ghrelin, and kisspeptin on the microRNA expression in separated NK cells. All of these hormones are able to effectively modulate the expression of microRNAs both stimulating and suppressing the cytotoxic potential of NK cells and thereby indirectly regulate the functions of these lymphocytes.

Hormonal regulation of NK cell cytotoxic activity.

The effects of chorionic gonadotropin, estriol (E), leptin, ghrelin, and kisspeptin on the intracellular expression of perforin, granzyme A, and granzyme B was studied in separated NK cells. All studied hormones except E are could modulate the expression of cytotoxic enzymes in NK cells by suppression of the expression of the most active proapoptotic agents, resulting in increased expression of granzyme A, which is typical of the decidual subpopulation of these lymphocytes.

Roles of leptin and ghrelin in the regulation of the phenotype and cytokine production by NK cells from peripheral blood.

Both leptin and ghrelin used separately at the concentrations corresponding to trimesters II-III of pregnancy increase the number of CD56 NK cells in mononuclear cell suspension; their combination also enhances the L-selectin expression on the surface of these cells in the culture. These hormones do not affect the production of TGF-β1, IL-17А, or IFN-γ by NK cells, and they inhibit the production of IL-10. Leptin decreses the IL-4 production by NKp46 cells, but the presence of ghrelin abrogates this effect.

[The Influence of Chorionic Gonadotropin and Estriol on NK Cells Phenotype and Functional Activity.].

The influence of chorionic gonadotropin (CG) and estriol (E3) at concentrations typical of pregnancy on the expression of phenotypic markers and cytokine production by separated NK cells were studied. It is found that these hormones increase the percentage of CD56brightL-selectin+ NK-cells, but also stimulate the expression of the inhibitory molecule NKG2A in the lymphocytes. In addition, E3 and CG stimulate the production of TGF-B, inhibiting the secretion of all other cytokines by separated NK cells.

Oligopeptides of Chorionic Gonadotropin β-Subunit in Induction of T Cell Differentiation into Treg and Th17.

The role of oligopeptides of chorionic gonadotropin β-subunit (LQGV, AQGV, and VLPALP) in induction of differentiation into T-regulatory lymphocytes (Treg) and IL-17-producing lymphocytes (Th17) was studied in an in vitro system. Chorionic gonadotropin and oligopeptides promoted CD4(+) cell differentiation into functionally active Treg (FOXP3(+)GITR(+) and FOXP3(+)CTLA-4(+)), while chorionic gonadotropin and AQGV additionally stimulated IL-10 production by these cells. In parallel, chorionic gonadotropin and oligopeptides prevented CD4(+) cell differentiation into Th17 lymphocytes (ROR-gt(+)IL-17A(+)) and suppressed IL-17A secretion.

The effect of kisspeptin on the functional characteristics of isolated NK cells.

The effect of kisspeptin at concentrations typical of pregnancy on the functional activity of isolated cytokine-primed NK cells has been investigated. The hormone has been shown to promote an increase in the proportion of CD56(bright) NK cells, as well as an increase in the L-selectin expression on the cell surface. Assessment of cytokine levels has shown that kisspeptin suppresses the production of IL-4, IL-10, and IFN-γ while stimulating the production of TGF-β by isolated NK cells.

[Effect of Escherichia coli secreted metabolites on functional activity of human neutrophils against the background of estriol effect].

Aim: Study the effect of Escherichia coli acellular metabolites of various phases of development on phagocytic activity of neutrophils against the background of pregnancy hormone effect--estriol (E3).

Materials And Methods: E. coli K12 (wt) metabolites were selected at the end of adaptation and logarithmic growth phases by filtration after cultivation at 37 degrees C in LB broth.

Role of leptin and ghrelin in induction of differentiation of IL-17-producing and T-regulatory cells.

We studied isolated and combined effects of leptin and ghrelin on the formation of IL-producing and T-regulatory cells. Leptin in concentrations comparable with its normal blood concentration during pregnancy (trimester II-III) promotes differentiation of peripheral blood CD4(+) cells to IL-17-producing cells and enhances IL-17A production, but suppresses the formation of T-regulatory cells in vitro. In contrast, ghrelin in a concentration typical of trimester I-II of pregnancy reduces the number of IL-17-producing cells, but stimulated the formation of T-regulatory cells.