The First Genome from the Basal Monocot Family Has Been Misnamed: Taxonomic Identity of Acorus tatarinowii (Acoraceae), a Source of Numerous Chemical Compounds of Pharmaceutical Importance

The basalmost monocot genus Acorus is well-known for its use in traditional oriental medicine. It comprises the groups of A. calamus and A. gramineus. A recent study recognized three species in the latter group, A. gramineus, A. macrospadiceus, and A. tatarinowii. The material currently known as A. tatarinowii has been extensively studied as a source of various chemical compounds and for producing the first published genome of Acorus, which is important for understanding the origin and evolution of monocots. Using the data from morphology, anatomy, and biogeography, we argue that the type material of A. tatarinowii does not match the interpretation of the species name as adopted in the current literature and herbarium collections (to a taxon of the A. gramineus group from Southeast Asia) but rather belongs to the A. calamus group. Moreover, the name A. macrospadiceus also cannot be used because it was invalidly published. Under a narrow species concept, other appropriate species names should be found or proposed for the plants currently named A. tatarinowii and A. macrospadiceus. However, we discourage the use of a narrow species concept in the A. gramineus group as insufficiently justified and suggest recognizing a single polymorphic species, A. gramineus s.l., at least until a comprehensive taxonomic revision of the group is available. Apart from the presentation of our revised taxonomic framework, we update the geographical distributions of Acorus species in Vietnam, Laos, and Thailand

Cellular mechanisms for maintenance of feto-maternal tolerance during pregnancy

Pregnancy is an immunological paradox, since a fetus carrying paternal antigens is a semiallogeneic transplant that should be rejected by the mother’s body. However, the fetus is completely protected from immune attack, thus suggesting some complex mechanisms of feto-maternal interaction. Hormonal, autocrine and paracrine immune signals and neuronal pathways play an important role in the development and maintenance of pregnancy. Pregnancy is considered a dynamic and actively modulated immunological process at each stage of pregnancy, including embryo implantation, placentation, fetal development, and delivery, being represented by a unique immune status. Studying the mechanisms of maintenance of pregnancy is vital to address the problems of miscarriage of unknown etiology. Successful pregnancy is closely related to the ability of the maternal immune system to properly adapt for each distinct stage of gestation. This review considers the main cell populations, such as regulatory subtypes of T and B cells, T helper cells, decidual natural killers, myeloid suppressors, erythroid nucleated cells which provide feto-maternal tolerance via various intercellular and humoral mechanisms. Maternal immune cells in the placenta do not attack fetal cells (trophoblasts) due to the tolerogenic microenvironment created by regulatory T cells and other immune cells. During pregnancy, each subpopulation of T helper cells plays a key role in promotion of fetal development through the production of angiogenic factors, providing immune surveillance and suppressing aberrant effector cell responses against a semi-allogeneic fetus. Accumulation of myeloid suppressor cells is especially relevant, when the immune tolerance is required for survival. Decidual NK cells closely interact with trophoblast cells and secrete cytokines that promote growth, mediate differentiation, trophoblast invasion, and remodeling of the spiral arteries. The favorable tolerogenic state in utero predisposes the newborn to severe infections, especially those caused by intracellular pathogens. Hence, the fetal tolerance may differ from other types of tolerance due to the presence of various immunosuppressive cells, such as erythroid suppressor cells in newborns. In the course of pregnancy, the properties of these cells change dynamically in order to meet the demands that arise during pregnancy in a timely manner. Understanding the immunological changes induced by pregnancy may not only reveal new therapeutic strategies to improve pregnancy outcomes, but also highlight new aspects of how the immune tolerance works being applicable in other physiological and pathological contexts

Modern T cell technologies for immunotherapy of solid tumors

According to the common concept of immune editing, the interaction of malignant tumor cells and immune system is a complex multifactorial process, which may result in both antitumor effector activity and development of suppressor mechanisms that promote tumor growth. Accumulation of scientific knowledge in the field of studying the antitumor immune response and tolerance has led to emergence of many research and therapeutic approaches that use different components of the immune system to combat neoplastic processes. Along with currently available approaches, there are strategies that use the potential of antigen-specific T lymphocytes, the main effectors of adaptive immunity, in order to fight malignant neoplasms which appeared more than a century ago and have built the scientific basis of cancer immunotherapy. One line of evidence of the significant antitumor potential of T cells in immunotherapeutic schemes for the cancer treatment was presented by successful therapy of hemato-oncological diseases, achieved at the end of the past decade. At the same time, however, the therapy of solid malignant neoplasms still faces significant difficulties that limit the efficiency of treatment. In this regard, the main objective of the review is to accumulate up-to-date information on the successes and limitations of T cell immunotherapy in the patients with solid tumors. To date, the phenotype and functionality of T cells is being investigated and modulated both towards enhancing antitumor cytotoxicity, increasing viability and proliferative activity of T cells, and in overcoming the immunosuppressive effect of the tumor and its tolerogenic microenvironment upon T cells, as well as ensuring targeted migration of the effector T cells to the malignant tissues. This review discusses immunotherapeutic approaches exploiting the potential of effector T lymphocytes, e.g., current clinical trials or applied therapeutic regimens for the treatment of solid malignant neoplasms. Antigen-independent approaches aimed at nonspecific enhancement of the T cell responses, i.e., therapy with recombinant cytokines and inhibition of immune checkpoint molecules. Antigendependent, or antigen-specific approaches such as adoptive T cell therapy with endogenous T lymphocytes are also discussed as well as trials on T cells with modified antigen-recognition receptor (CAR-Tcells, TCR-Tcells), like as usage of bispecific antibodies as T cell engagers. The review describes the benefits and disadvantages of these approaches in monotherapy, as well as current results and prospects for their mutual combinations

Study of phenotypic and cytotoxic properties of erythroid cells of the spleen under hematopoiesis-stimulating effects

In recent years, research has revealed a wide variety of erythroid cell functions, including modulation of innate and adaptive immune responses. Anemic or hypoxic stress stimulates a physiological response in the form of stress erythropoiesis, aimed at increasing oxygen delivery to tissues. Stress erythropoiesis activates progenitor cells and uses mechanisms that differ from stationary bone marrow erythropoiesis. To consider the role of erythroid cells in the regulation of hematopoiesis, hematopoiesis-activating states were modeled: chemically induced hemolytic anemia, acute blood loss, hypoxia. A series of experiments was carried out on first-generation hybrid mice CBA C57Bl6. Isolation of erythroid cells was performed using magnetic separation for the CD71 marker. The stages of differentiation of erythroid cells were determined by the combination of expression of TER-119 and CD71 markers and direct light scattering parameters in the population of both CD45-positive and CD45-negative spleen cells. To study the immunoregulatory activity of erythroid cells, we investigated the mediated cytotoxicity of splenocytes against tumor cells of the mouse melanoma B78 line after cultivation with conditioned spleen media after various hematopoiesis-stimulating effects. With various hemopoiesis-stimulating effects, the quantitative and qualitative composition of the spleen cells is reorganized depending on the compensatory mechanism for restoring homeostasis. An analysis of the cellular composition of the spleen showed that under hematopoiesis-stimulating effects, a redistribution of populations with the CD45 marker occurs: during hypoxia, the number of CD45-negative cells sharply decreases and the number of CD45-positive cells increases. The population of basophilic erythroblasts is the least susceptible to quantitative changes under all hematopoiesis-stimulating effects. During hypoxia, the most noticeable change in the cellular composition of the spleen is observed due to the increased accumulation of CD45-positive erythroid cells in the spleen. Mediators of erythroid cells of the spleen of mice after hypoxia do not lead to an increase in the cytotoxic proapoptotic effect of splenocytes on tumor cells, in contrast to the erythroid cells of the normal spleen, spleen with anemia and blood loss. Thus, it is tissue hypoxia that is the process that not only stimulates erythropoiesis, but also leads to the maximum change in the suppressive properties of surrounding cells. We assume that the implementation of compensatory mechanisms under the studied hematopoiesis-stimulating effects is aimed at activating the mechanisms of innate immunity and local immunosuppression to prevent local inflammation, accumulate nutrients, and attract cellular elements to the focus of hematopoiesis to restore homeostatic functions

Association of Single Nucleotide Polymorphisms in the IL-18 Gene with Production of IL-18 Protein by Mononuclear Cells from Healthy Donors

IL-18 has proinflammatory effects and participates in both innate and adaptive cellular and humoral immunity. A number of SNPs that influence IL-18 production are found in the gene promoter region. We investigated the association of SNPs in the IL-18 promoter at −607 and −137 with the level of IL-18 protein production by PBMC from healthy donors from Southwestern Siberia. The genetic distribution of these SNPs in the promoter site was established by PCR. IL-18 protein production was determined by ELISA. Our results showed that PBMC from donors carrying allele 137C have lower levels of both spontaneous and LPS-stimulated IL-18 production. In contrast, PBMC from donors carrying allele 607A showed significant increases in spontaneous and stimulated IL-18 production compared to wild type. Our study suggests that the SNPs −607 and −137 in the promoter region of the IL-18 gene influence the level of IL-18 protein production by PBMC from healthy donors in Southwestern Siberia

TUMOR NECROSIS FACTOR-α MEMBRANE-BOUND AND SOLUBLE RECEPTORS IN NORM AND IN RHEUMATOID ARTHRITIS

TNFα — a multifunctional pleiotropic cytokine, considered to have a special significance in the immunopathogenesis of rheumatoid arthritis. Herewith the effectiveness of immunomodulatory cytokine and its role in the development of pathological states of the organism may depend largely on the content of soluble receptors and expression of membrane-bound receptors. The study shows several significant differences not only in the percentage of cells with. TNFα receptors, but also in the absolute number of receptors expressed on cells from different subsets of immunocompetent cells in health and in rheumatoid arthritis, establishes correlation relationships of these parameters with serum contents of the cytokine and its soluble receptors. The mechanisms and the role of changes in the expression of TNFα receptors in different subsets of leukocytes in immunopathological state and in compare with healthy donors are discussed

SERUM LEVEL AND PRODUCTION OF CYTOKINES BY PBMC IN PATIENTS WITH ATOPIC DERMATITIS

The рарег presents the results of measurements of cytokine levels in serum and conditioned medium of PBMC cultures from the patients with atopic dermatitis with the exacerbation and remission in comparison with the healthy donors. We have shown that the serum levels of the key cytokines IL-5 and IL-13, proinflammatory cytokines IL-1β and IL-6 and the main Th1 cytokine — IFNγ — were higher compared to healthy donors. In the conditioned media of peripheral blood mononuclear cells in contrast, we have found a significant decrease of the spontaneous secretion of key cytokines IL-10 and IL-17. We have shown that the stimulated secretion of IL-5 and IL-13, IL-12 and INF-γ is significantly reduced in comparison with the control level. Only IL-1β revealed a statistically significant higher level of stimulated secretion without exacerbation of atopic dermatitis. The contemporary therapy has no effect on cytokine production

EXPRESSION DENSITY OF RECEPTORS FOR IMMUNOREGULATORY MEDIATORS AS A MODULATORY COMPONENT OF BIOLOGICAL EFFECTS OF MEDIATORS UPON CELLS (PART 2)

The present review article summarizes the latest world scientific data on the role of receptors for immune mediators in regulating biological effects on the cells. For the main classes of immune regulators (interleukins, interferons, growth factors and tumor necrosis factors), the variants are presented for participation of receptors as components of cytokine/cell interaction, as proven by in vitro and in vivo studies. Ability of the receptors expression to modify characteristics and type of these interactions is shown. The data on participation of receptors for regulatory molecules in development of immune-mediated diseases of various genesis have been analyzed. It was demonstrated that the changes in the receptor expression are of great importance when evaluating functional response of the cells to the mediators and in development of pathological conditions. Current studies confirmed the data suggesting effects of receptor density upon the processes of proliferation and apoptosis, as well as metabolic processes that trigger development of autoimmune, oncological and dystrophic diseases. For all the considered classes of regulatory molecules, the change in the density of receptor expression is one of the key aspects in regulating functional activity of the cells. Thus, studying expression levels of receptors on the cell membrane is important in understanding pathogenesis, whereas changing expression level may be considered as a therapeutic target in the treatment of various diseases

EFFECT OF DNA CONSTRUCTIONS ELECTROPORATION ON DENDRITIC CELLS

Today transfection of mammalian cell with DNA or RNA construction is the only method for delivering programmed information into the cell nucleus. Electroporation is most commonly used method of transfection in experiments with dendritic cell. The aim of electroporation is to permeabilize the membrane by passing electric impulse through the cell. Due to the increase permeability of the membrane chance DNA or RNA construction getting inside into the cell is increased, wherein survival of the cells is decreased.In the study male mice C57Bl/6 line 2-4 months old were used. From femur bones was isolated 20 × 106 bone marrow cells, which were cultured in 20 mL of complete RPMI-1640 for 7 days. To generate dendritic cells from BM cells, 100 ng/mL of rmFlt3-L was added to culture media at day 0. After 7 days of cultivation, the cell cultures were electroporated with control noncoding plasmids p5 (EP P5) or pmaxCCR9 encoding mouse chemokine receptor CCR9 (EP CCR9). The controls were cell cultures electroporated without any plasmids (mock EP) and cell cultures without electroporation (none EP). 5 × 105 cells were electroporated and resting for 10 minutes. After 10 minutes, cells were harvested and seeded into 24-well plates in 1 mL of culture medium and conditioning medium (1:1). Then, 50 ng/mL of Flt3-L was added to each well. The next day, transfected cells were collected and used for flow cytometry, qRT-PCR analysis.It was found that after electroporation in the groups mock EP, EP P5, EP CCR9 relative amount of live CD11c+ dendritic cells was significantly less than in the non EP group. Moreover, in the EP P5 and EP CCR9 groups the frequency of live CD11c+ dendritic cells was significantly less than in the mock EP group. Expression of the CD86 marker in the EP P5 and EP CCR9 groups was significantly higher than in the non EP and mock EP groups. Expression of the I-AB(MHCII) in the EP CCR9 group on cDC2s was significantly higher than in the non EP group. On plasmacytoid DCs (pDCs) and conventional type 2 DCs (cDC2s) in the EP CCR9 group expression of CCR9 was significantly higher than in the non EP group. Therefore, in this study, we demonstrated the effectiveness of electroporation, accompanied by the decrease in the survival rate and maturation of DCs