Medical Immunology (Russia)最新文献

{"title":"The significance of notch signaling in the regulation of Тreg-lymphocyte differentiation in patients with infiltrative pulmonary tuberculosis","authors":"A. E. Sanina, V. Serebryakova, O. Urazova, A. Gadzhiev, Т. E. Kononova","doi":"10.15789/1563-0625-son-2676","DOIUrl":"https://doi.org/10.15789/1563-0625-son-2676","url":null,"abstract":"Data on the role of regulatory T lymphocytes (Treg) in the immunopathogenesis of tuberculosis are actively accumulating in the current literature. The overwhelming effect of Treg cells on the proliferation, functional activity of Th1 lymphocytes and antigen-presenting cells allows to consider this population as a possible target of modulation of the immune response in patients with tuberculosis. The Notch signaling pathway participates in the regulation of FoxP3 transcription factor expression and, therefore, is capable of supporting suppressor activity of Treg lymphocytes. A key role in the functioning of the Notch signaling cascade belongs to the enzyme γ-secretase that cleaves the intracellular domain of the receptor (Notch ICD), with the subsequent formation of a complex that regulates cell differentiation. The actively studied inhibitor of γ-secretase is DAPT – N-[N-(3.5-difluorophenacetyl)-L-alanyl]-S-phenylglycine tert-butyl ester). Mononuclear leukocytes isolated from the blood of patients with drug-sensitive and drug-resistant pulmonary tuberculosis by gradient centrifugation before the start of anti-tuberculosis therapy were used as the material for the study. The cells were cultured under conditions of stimulation with Mycobacterium tuberculosis antigens CFP10-ESAT6 or with the addition of γ-secretase inhibitor (DAPT) at doses of 5 μM/L and 10 μM/L in combination with CFP10-ESAT6 at 37 °C and 5% CO2 for 72 h to the incubation medium. The number of Treg lymphocytes was assessed by flow cytofluorimetry by determining the expression of the CD4 surface receptor (FITC) and the intracellular transcription factor FoxP3 (PE). In intact cell cultures of pulmonary tuberculosis patients, the relative number of Treg lymphocytes was statistically significantly (p < 0.001) higher than that of healthy donors. Stimulation of cells with CFP10-ESAT6 antigens was accompanied by an increase in the proportion of CD4+FoxP3+ cells in both groups of tuberculosis patients. Addition of γ-secretase inhibitor at a concentration of 5 μM/L to the incubation medium did not lead to statistically significant changes in the number of Treg lymphocytes. The increase in DAPT concentration up to 10 μM/L was accompanied by a decrease in the number of Treg lymphocytes in comparison with the corresponding indices upon stimulation with CFP10-ESAT6 antigens in all groups of the subjects. Regardless of cultivation conditions, the number of CD4+FoxP3+ cells in patients with drug-resistant mycobacteria exceeded their number in patients with drug-sensitive pulmonary tuberculosis. Inhibition of the Notch signaling pathway by a γ-secretase inhibitor (DAPT) at a concentration of 10 μM/L contributed to a decrease in the number of Treg lymphocytes in patients with drug-sensitive and drug-resistant pulmonary tuberculosis. Reduction of Treg lymphocyte number by γ-secretase inhibitor confirms the importance of Notch signaling cascade as a potential target for correction of Treg lymphocytes","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"74 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86322381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of morphogenic proteins of the WNT signaling pathway in coronary artery disease","authors":"I. Snimshchikova, M. Plotnikova","doi":"10.15789/1563-0625-rom-2835","DOIUrl":"https://doi.org/10.15789/1563-0625-rom-2835","url":null,"abstract":"In recent years, researchers’ attention has been directed to the WNT signaling pathway study, which regulates embryogenesis processes and is involved in pathological condition development. The role of morphogenic proteins of WNT signaling pathway in the cardiovascular pathology genesis is practically not clear. The research aim was a comprehensive study of the main proteins of WNT signaling pathway (β-catenin, sclerostin, GSK-3α, GSK-3β, WIF-1 and DVL-1) in the blood serum of 353 patients with coronary artery disease acute forms who were treated at the Orel regional vascular center from 2019 to 2021, and 50 healthy individuals. A comprehensive analysis included an assessment of clinical, laboratory and instrumental parameters in the framework of current clinical guidelines, as well as an immunological examination to determine the morphogenic proteins of WNT signaling by enzyme immunoassay. The results showed a wide variability in the values of morphogenic proteins of WNT signaling pathway in the patient’s blood serum. The levels of β-catenin, WIF-1 and DVL-1 significantly exceeded those obtained in healthy individuals, while the concentrations of sclerostin and GSK-3β did not differ significantly from them. The level of GSK-3α of patients was twice lower than in healthy individuals. The highest sclerostin concentrations were found in patients with existing calcification of the aortic valve leaflets and aortic walls. Acute coronary syndrome unfavorable course was observed in patients with both extremely high and extremely low WIF-1 levels. Significant correlations were established between the level of morphogenic proteins of WNT signaling pathway and lipid metabolism, as well as myocardial remodeling. The obtained data on changes in the protein production of WNT signaling pathway allow us to expand our understanding of the molecular aspects of the immunopathogenesis of myocardial remodeling in coronary artery disease, increase the predictive potential for cardiovascular disease diagnosis and determine the vector for further development of cardioimmunology determination.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86427462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blood platelets in chronic graft-versus-host disease: association with Th1/Th2 ratio","authors":"О. P. Kolesnikova, Е. V. Goiman, I. Orlovskaya, Е. N. Demchenko, N. Volskiy, Е. D. Gavrilova","doi":"10.15789/1563-0625-bpi-2708","DOIUrl":"https://doi.org/10.15789/1563-0625-bpi-2708","url":null,"abstract":"As found in clinical and laboratory studies, platelets not only play a key role in the processes of coagulation and thrombosis, but are also able to actively participate in other pathophysiological processes, including the development of immune reactions. It has been shown that changes in the immune system leading to systemic lupus erythematosus (SLE) are often accompanied by changes in the number of platelets and their activity in the peripheral blood of SLE patients, which correlate with the severity of the clinical manifestations of the disease. Earlier we have studied the standard experimental model of SLE in detail, based on the induction of chronic graft-versus-host disease (cGVHD) in the semi-allogeneic system DBA/2 → (C57Bl/6 x DBA/2)F1. However, the participation of platelets in this immunopathological process has not been studied. There are no data in the literature on the behavior of platelets in cGVHD or on their relationship with the state of Th1/Th2 balance. It can been expected that the platelet count changes according to the development of cGVHD in the used experimental model by analogy with the development of SLE in humans.In the experiments, we used female mice of the DBA/2 strain and (C57Bl/6 × DBA/2)F1 hybrids. Chronic GVHD in a semi-allogeneic system was induced by injecting DBA/2 mouse splenocytes into B6D2F1 hybrid mice: 60-70 × 106 cells intravenously twice with an interval of 6 days. The studied parameters were evaluated three months after the start of the experiment and the formation of lupus-like glomerulonephritis in animals with Th2-dependent cGVHD variant.A decrease in the number of erythrocytes and hemoglobin, a decrease in hematocrit and a parallel increase in the number of reticulocytes in the blood of mice with cGVHD are in good agreement with our earlier conclusion that these animals have autoimmune hemolytic anemia. It was found that, platelets increase significantly with the development of cGVHD unlike other blood cells. Secondary thrombocytosis is observed in the case of the Th2-dependent variant of сGVHD in this model of SLE, while in the group with the Th1-dependent variant of сGVHD, the average number of platelets in the blood does not differ from the control group.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83739836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypoxia-induced factor-1α and markers of inflammation in patients with ischemic stroke","authors":"L. Pivovarova, I. Voznyuk, I. V. Osipova, O. Ariskina, E. A. Gogoleva, M. V. Prokhorova, N. G. Karpova","doi":"10.15789/1563-0625-hif-2740","DOIUrl":"https://doi.org/10.15789/1563-0625-hif-2740","url":null,"abstract":"Ischemic stroke (IS) occurs as a result of local disturbance of hemocirculation and hypoxia in the brain tissue. Hypoxia-inducible factor-1α (HIF-1α), which is involved in the regulation of tissue oxygen levels, plays an important role in the pathophysiology of stroke, including neuronal survival, neuroinflammation, angiogenesis, glucose metabolism, blood-brain barrier permeability, and is important in IS outcomes. The purpose of the study was to determine the relationship between blood levels of HIF-1α and the degree of neurological deficit in the acute period of IS and the outcome of the disease. We examined 58 people with IS aged 73 (67-81) years. Patients were divided into two groups – discharged and dead. The severity of stroke (NIHSS), neurological deficit, comorbidity index, blood levels of HIF-1α, p53 protein, interleukin-6, cystatin C, CRP, creatinine, hematological parameters were determined at admission, on days 3 and 10 of the disease. At admission the blood levels of HIF-1α was lower than in the comparison group and remained reduced until the 10th day. On day 10 the association of HIF-1α with neurological deficit, comorbidity index and disease outcome was determined. We observed a feedback of HIF-1α with the content of erythrocytes, hemoglobin and hematocrit, which can be regarded as a reflection of the hemic component of mixed hypoxia. In dead patients, an increased blood level of cystatin C was detected, which was associated with HIF-1α concentrations. In all periods of observation of IS, a correlation between cystatin C and creatinine and CRP levels was noted. These results may indicate dysfunction of endotheliocytes, inflammation associated with hypoxia in IS. The prognostic significance of the blood level of HIF-1α on the 10th day for the outcome of IS was AUC = 0.900. Blood levels of HIF-1α in the acute period was associated with the severity of IS and the outcome of the disease.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76889028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of pregnancy-specific β1-glycoprotein on myeloid-derived suppressor cell differentiation","authors":"V. Timganova, K. Shardina, M. Bochkova, S. Uzhviyuk, D. Usanina, S. Zamorina","doi":"10.15789/1563-0625-eop-2838","DOIUrl":"https://doi.org/10.15789/1563-0625-eop-2838","url":null,"abstract":"Myeloid-derived suppressor cells (MDSCs) are a heterogeneous cell population that primarily suppress T lymphocytes in healthy pregnancies and pathologies. MDSCs are one of the key regulators of immune responses. Finding ways to control them is important for the treatment of cancer, autoimmune diseases, miscarriage, and post-transplant complications. The mechanisms of immune suppression by MDSC are: expression of CD73, ADAM17, PD -L1, production of Arg 1, iNOS, IDO, IL -10 and TGF-b1.Pregnancy-specific b1-glycoprotein (PSG) has modulatory effects on dendritic cells and macrophages that mediate the shift of T cell phenotypes toward Th2 and Treg. We have previously shown that native PSG suppresses Th17 differentiation and cytokine production, stimulates the production of IDO by monocytes and the differentiation of Tregs.Considering the immunomodulatory properties of PSG and the key role of MDSCs in pathologies, the aim of our work was to investigate the effect of native and recombinant PSG on the differentiation of MDSCs in vitro.MDSCs were differentiated from CD11b+ peripheral blood cells. Cells were cultured for 7 days and received stepwise GM-CSF, IL-1b, and LPS. Native (n) (1; 10 and 100 mg/mL) and recombinant (r) (1 and 10 mg/mL) PSG were introduced into the cultures three days before the end of incubation. Flow cytometry was used to determine the percentage of MDSC among the cells in culture and the percentage of M-, PMN-, and e-MDSC among the total number of MDSCs.It was found that rPSG (1 mg/mL) increased the percentage of MDSCs in culture. Both nPSG (1 and 10 mg/mL) and rPSG (10 mg/mL) increased the proportion of M-MDSC, whereas rPSG (10 mg/mL) decreased the number of PMN-MDSC.Thus, the cytokine background in CD11b+ cell cultures favored the differentiation of predominantly M-MDSC, similar to the tumor microenvironment, whereas native and recombinant PSG enhanced this effect. Thus, nPSG and rPSG are able to modulate the differentiation of MDSCs by increasing their number, mainly due to the monocytic subpopulation. This fact opens perspectives for new research on targeted manipulation of MDSCs.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88384697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of proinflammatory cytokines in Hashimoto's thyroiditis associated with psychiatric disorders","authors":"P. Sobolevskaia, A. N. Gvozdeckii, I. Kudryavtsev, V. Chereshnev, L. P. Сhurilov","doi":"10.15789/1563-0625-rop-2812","DOIUrl":"https://doi.org/10.15789/1563-0625-rop-2812","url":null,"abstract":"Mental disorders often accompany autoimmune diseases, for example, since 1949 it has been known about “myxedematous madness”, a psychosis caused by hypothyroidism. The most common cause of hypothyroidism is Hashimoto's autoimmune thyroiditis. It is also known about another neuropsychiatric disorder associated with autoimmune thyroiditis, Hashimoto's encephalopathy. It is a severe dysfunction of the central nervous system, the pathogenesis of which is not associated with hormonal disorders. Cytokines are regulators and participants of inflammation, including autoimmune. Certainly, when we are talking about high concentrations cytokines, we mean systemic inflammation. The minimal or mediocre fluctuations in cytokines within the ranges that are characteristic of healthy status or normergic acute phase response in disease cannot be interpreted from the point of view of binary endocrinological logic. In the CNS, cytokines are able to influence on the neuroendocrine control of systemically regulated functions. It is also important that glial cells (astroglia, microglia) are capable of producing a number of cytokines and can affect neurons and develop behavioral changes. In addition, the ability of a number of cytokines outside the CNS itself to act on vagal afferents and through them to convey information to the CNS, affecting its state and functions, has been proven. It is reasonable to assume that minimal fluctuations in cytokine levels may also affect the state and function of the CNS. The aim of the study was to investigate the levels of cytokines in patients with thyroiditis; in patients with thyroiditis associated with mental disorders; in a group of healthy individuals; and evaluate the effect of cytokine levels on clinical manifestations. In the group of patients with thyroiditis and mental disorders, the levels of CCL20/MIP3α, IL-13, IL-2, IL-27, IL-5 were significantly higher than in other groups. At the same time, no positive correlation was found between the clinical manifestations of mental disorders and the levels of cytokines. A positive correlation was found between the levels of some cytokines and free triiodothyronine, as well as the level of antithyroid antibodies. Mental disorders associated with autoimmune thyroiditis may be associated with changes in the cytokine profile and result from neuroinflammation.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73730083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cholecalciferol as a means of nonspecific immunoprophylaxis against COVID-19","authors":"O. V. Berdiugina, E. Gusev","doi":"10.15789/1563-0625-caa-2849","DOIUrl":"https://doi.org/10.15789/1563-0625-caa-2849","url":null,"abstract":"The current direction of scientific research in recent years has been the study of the immunobiological properties of vitamin D. The purpose of this work was to analyze the results of oral administration of cholecalciferol in order to prevent infection with the SARS-CoV-2 virus in the first wave of the COVID-19 pandemic. The study was performed in the period from October 07 to December 29, 2020, when there were no immunobiological drugs for specific prevention of COVID-19. The total number of respondents was 73 people; all had been ill with coronavirus only once. The etiological diagnosis of the disease included molecular genetic testing of samples of two localizations obtained by the conventional method (nasopharynx, oropharynx). The concentration of antibodies to the virus was determined on average 2 months after the disease using a set of reagents SARS-CoV-2-IgG quantitative-ELISA-Best (JSC Vector-Best, Russia). An approximate assessment of IgM concentration was carried out using a set of SARS-CoV-2-IgM-ELISA-Best from the same manufacturer. Among the study participants were those who used immunobiological drugs for the prevention of infection (riamilovir, umifenovir hydrochloride monohydrate, human recombinant interferon alpha-2b, zinc acetate, vitamin C). In particular, 28 people (38.4%) took cholecalciferol (group No. 1) and 45 people (61.6%) did not use this (group No. 2). Statistical processing of the obtained data was performed using the statistical package STATISTICA v.12.5.192.5 (StatSoft, Inc., USA). We applied the analysis of basic statistics, Linear Discriminant Analysis, Kolmogorov–Smirnov test, Chi-Square test, Wald–Wolfowitz Runs Test, Kruskal– Wallis test. Differences in the incidence of respiratory distress syndrome of the two studied groups were revealed: in patients taking cholecalciferol, the syndrome did not develop at all; in group No. 2, it was registered in 20.0% of cases (Chi-Square = 5.242, p = 0.02). In addition, in patients of group No. 1, the concentration of IgG 2 months after the disease was 3.8 times higher than the values in group No. 2 (Chi-Square = 9.268, p = 0.003). Similar differences were found for the IgM level (Wilks' Lambda: 0.659 approx. F (7.32) = 2.367 p < 0.045). It was known that in both groups there were respondents who used other immuno-active substances for preventive purposes. In the first group there were 18 people (24.7% of all); in the second, there were 13 people (17.8% of all). It was found that those who used other immuno-active substances and did not take vitamin D suffered the disease more easily than everyone else. The respondents who did not use any immunoprophylactic agents were the next in terms of the severity of the infection. The respondents who took cholecalciferol mainly assessed the severity of the infection as average. The study participants who took both vitamin D and used other means of prevention suffered the most from COVID-19. Respondents who took cholecalciferol more oft","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74486574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Features of changes in the expression level of TNFα receptors and the functional response of cell lines upon stimulation with various doses of cytokine","authors":"Yu. A. Lopatnikova, Y. Zhukova, A. Alshevskaya, I. Obleukhova, F. Kireev, I. Belomestnova, S. Sennikov","doi":"10.15789/1563-0625-foc-2718","DOIUrl":"https://doi.org/10.15789/1563-0625-foc-2718","url":null,"abstract":"TNFa is a pro-inflammatory cytokine that is signaled through type 1 (TNFR1) and type 2 (TNFR2) receptors. TNFR1 normally mediates apoptosis, cell survival, and cytokine secretion, while TNFR2 selectively mediates cell survival and cytokine secretion. But in some cases, when receptors are activated, the functional response of cells changes to the opposite. Activation of signaling pathways has its own triggers, which differ in the interaction between different forms of cytokine and different forms of receptor complexes, as well as changes in the ratio of different types of receptors. The study of the mechanisms of regulation in the ligand-receptor system is a priority task for many studies. This work shows the dose-dependent effect of TNFa on the expression of cytokine receptors and changes in the functional response of tumor cell lines of various origins. For this, a comparative assessment of the expression and co-expression of receptors, cell cycle phases and apoptosis of cell lines without stimulation and stimulated with TNFa at concentrations of 5 and 50 ng/mL was carried out. It was found that the K562 cell line was characterized by more pronounced changes in receptor co-expression, which were observed at a TNFa concentration of 50 ng/mL compared to both the control group and the 5 ng/mL group. The decrease in the relative content of cells expressing only TNFR1 was combined with a decrease in the percentage of cells in apoptosis, which confirms the literature data on the role of this receptor in the development of apoptosis. At the same time, no changes in expression density were observed for this cell line. For the ZR75-1 cell line, the largest number of effects was also found for a TNFa concentration of 50 ng/mL. An increase in the relative content of cells expressing only TNFR2 was combined with an increase in apoptosis; however, the expression density of this type of receptor was low, which could affect the switching of signaling pathways towards proapoptotic ones. Thus, our study allowed us to reveal the features of changes in the expression and co-expression of TNFa receptors characteristic of cell lines of various origins, as well as changes in the functional response of cells in response to stimulation with different doses of cytokine. All this allows us to expand our understanding of the regulatory mechanisms in the cytokine-receptor system.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74440053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Features of parameters of cellular immune depending on the activity of foci of demyelination in children with multiple sclerosis","authors":"T. Radygina, D. Kuptsova, O. Kurbatova, S. Petrichuk, E. Semikina, A. Fisenko, L. M. Abdullaeva, B. Bursagova","doi":"10.15789/1563-0625-fop-2777","DOIUrl":"https://doi.org/10.15789/1563-0625-fop-2777","url":null,"abstract":"MS is a common disease of the central nervous system that leads to disability and reduced quality of life. The debut of disease in 3-5% of patients occurs in childhood and has a less favorable course compared to adults. MS is caused by the activation of autoreactive T cells in the breakdown of peripheral tolerance, which is normally controlled by regulatory T cells (Tregs). It is promising to study expression of CD39 and CD73 in Treg and Th17 populations to assess their suppressive activity. Aim is to evaluate content of major and minor lymphocyte populations and expression of CD39 and CD73 in CD4+ lymphocyte population in children with MS. 111 children with MS were examined, 66 with contrast-negative lesions on MRI (Group 1), 45 with contrast-positive lesions (Group 2). The comparison group consisted of 46 healthy children (Group 3). Content of T, B, NK lymphocytes, Treg (CD4+CD25highCD127low), Thact (CD4+CD25highCD127high), Th17 cells (CD3+CD4+CD161+); expression of CD39 and CD73 in Treg, Th17 and Thact was performed by flow cytometry. An increase in content of T helpers, a decrease in NK cells in patients in group 2 was revealed. An increase in number of Thact and Th17 lymphocytes was obtained in patients of both groups with MS. Number of Tregs in group 1 was significantly higher than in group 3. Ratio of cells expressing CD39 and CD73 in MS patients depended on lymphocyte population as well as in the group 3. The highest content of CD39+ cells was observed in Treg population, and the lowest in Thact population. For CD73 expression, on the contrary, the highest expression of CD73 was observed in Thact cells, the lowest in Treg. When comparing groups of patients, it was found that in patients of group 1, number of cells expressing CD39 ectonucleotidase was significantly increased, and number of supTh17 was comparable with group 3. In both groups of MS patients, an increase in CD73 counts in Treg, Thact and Th17 was observed. Thus, informative populations of lymphocytes (CD4+ cells, Treg, CD39+Treg, supTh17) have been identified, which can be used to monitor condition of children with multiple sclerosis.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74606893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Itaconate-mediated inhibition of succinate dehydrogenase regulates cytokine production in LPS-induced inflammation","authors":"D. E. Anisov, M. Drutskaya, M. A. Nosenko, S. Nedospasov","doi":"10.15789/1563-0625-imi-2841","DOIUrl":"https://doi.org/10.15789/1563-0625-imi-2841","url":null,"abstract":"Itaconate is an immunoregulatory metabolite produced by myeloid cells and plays a key role in the regulation of the immune response. Itaconate, on the one hand, is able to suppress the activity of succinate dehydrogenase (SDH), thereby making a significant contribution to the metabolic reprogramming of the cell. On the other hand, itaconate can regulate the activity of a number of transcription factors and transcription regulators, thereby affecting gene expression. In most experimental studies, itaconate has been characterized predominantly as an anti-inflammatory agent. In particular, itaconate produced by activated macrophages inhibits the production of cytokines TNF, IL-1b, IL-6, IL-10. However, some evidence suggests a pro- inflammatory role for itaconate in a number of mouse disease models. Thus, the deletion of the Acod1 gene responsible for the production of itaconate leads to the suppression of the production of TNF and IL-6 in the mouse polymicrobial sepsis model, which means that in the context of inflammation in vivo, itaconate can act as an inducer of pro-inflammatory cytokines. The mechanism of itaconate regulation of cytokine production in systemic inflammation remains unexplored. In this work, we have shown that injection of itaconate and its derivative dimethyl itaconate into mice, followed by induction of inflammation by bacterial lipopolysaccharide (LPS), leads to changes in the content of cytokines in the blood. Interestingly, the systemic production of IL-6 and IL-10 in response to itaconate is increased, contrary to the results previously obtained in cell cultures. At the same time, IFNg production, on the contrary, is suppressed. Apparently, itaconate regulates the production of cytokines in vivo by suppressing the activity of SDH. Injection of the SDH inhibitor, dimethylmalonate, followed by induction of inflammation in mice, results in similar changes in blood cytokines observed in response to itaconate: increased production of IL-6, IL-10 and suppression of IFNg production. On the contrary, the addition of succinate, a SDH substrate, leads to the opposite effect on cytokine production. Thus, it can be assumed that the observed effects of itaconate on cytokine production in the model of LPS-induced inflammation are mediated by its ability to inhibit SDH. These results help to understand the controversial role of itaconate in inflammation and shed light on a previously undescribed relationship between SDH and cytokine production in inflammation in vivo.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77597848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}