Cellular Links Research Articles

Influence of sleep on physiological systems in atherosclerosis.

Sleep is a fundamental requirement of life and is integral to health. Deviation from optimal sleep associates with numerous diseases including those of the cardiovascular system. Studies, spanning animal models to humans, show that insufficient, disrupted or inconsistent sleep contribute to poor cardiovascular health by disrupting body systems. Fundamental experiments have begun to uncover the molecular and cellular links between sleep and heart health while large-scale human studies have associated sleep with cardiovascular outcomes in diverse populations. Here, we review preclinical and clinical findings that demonstrate how sleep influences the autonomic nervous, metabolic and immune systems to affect atherosclerotic cardiovascular disease.

STATE OF CELLULAR IMMUNITY IN PURULENT CHOLANGITIS

Abstract. Objective: To study the state of the cellular link of immunity in acute and chronic cholangitis. Materials and methods. Cholangitis always worsens the condition of the biliary system. Depending on the magnitude of the pathological changes in the bile ducts, we distinguished three groups of patients. Group I – cholangitis caused by obstruction of the main extrahepatic bile ducts due to choledocholithiasis, group II – cholangitis in conditions of cicatricial strictures of the main bile ducts, and group III – cholangitis in conditions of already performed reconstruction of the duct system. The indicators of the cellular link of immunity were studied separately in each group. The results. The conducted studies indicate an imbalance of the immune system in patients with different courses of cholangitis. The presence of inflammation of a mild degree of severity causes stimulation of almost all links of the immune system, while the cellular branch reacts first. Conclusions. Long-term cholangitis was accompanied by suppression of the main markers of T-lymphocyte differentiation — CD2+, CD3+, CD4+ and CD8+, which take part in antigen presentation, signal transmission to other cells and affect their adhesive properties.

Analysis of immunopathogenesis of psoriasis in the dynamics of treatment

Оbjective — to analyze the parameters of the immune system of the organism in patients with psoriasis before and after treatment. Materials and methods. The parameters of cellular immunity in an organism estimated after the change of relative and absolute amount of T- (CD3+) and B- (CD19+) of lymphocytes and subpopulations (CD4+, CD8+, CD16+, CD25+, CD71+, CD30+, CD95+). To identify of surface structures of lymphocytes the method of direct immune fluorescence was used where fluorescent label was attached to anti-CD of mononuclear antibodies of series Leu of the firm «Becton Dikinson» (USA). Calculations were conducted on the laser instantaneous cytofluorometer of the firm «Baston» (USA). Results and discussions. The most positive influence on the parameters of the cellular link of the immune system of the organism was found in patients with psoriasis who received immunobiological therapy with the medication etanercept in combination with narrowband (311 nm) phototherapy. After treatment in patients of this group, due to a significant decrease in the production of TNF and its serum concentration, the pro-inflammatory changes in the cellular link of the immune system decreased, the number of lymphocytes with the an early activation marker, which initiated a further cytokine cascade of development and prolongation of inflammation decreased significantly. In addition, the established reduction in the number of CD30+ lymphocytes is an indirect factor indicating the switching of the Tx2 response (autoimmune manifestations) to Tx1, and hence the achievement of the clinical and immunological remission of the psoriatic process. It is extremely important for the functioning of the immune system the decrease in the content of activated lymphocytes that express the Fas-receptor as due to the increased lymphocyte apoptosis, namely, T-cytotoxic lymphocytes, and autoimmune and proliferative changes took place inherent in the exacerbation of the psoriatic process. Conclusions. It was established that all our schemes of psoriasis treatment have immunorehabiting properties but their degree of severity was different. The most effective treatment scheme is the combined use of etanercept and UVB therapy, thus proliferative and inflammatory changes in the skin reduced, antigenic loading decreased, the level of CICs, autosensibilization and autoimmune disorders also decreased.

Immune status of students with different levels of physical activity

The nature of changes in the immune system during physical work is a complex process involving many different mechanisms. Research in this direction is an urgent problem. The purpose of the research was to study the indicators of cellular and humoral immunity in students with different levels of physical activity. A total of 77 male students were examined, consisting of 3 groups: 1) with a low level of physical activity (n = 32) – students who were not involved in sports activities on a regular basis; 2) students with an average level of physical activity (n = 22) – beginner sambo wrestlers without sports categories; and 3) students with a high level of physical activity (n = 23) – highly qualified sambo wrestlers – first-class athletes, candidates for masters and masters of sports. In students of all groups, the quantitative content of various phenotypes of lymphocytes in the blood was studied by flow cytometry; serum immunoglobulin levels by laser nephelometry; phagocytic parameters by traditional methods; and oxygen-dependent metabolism of neutrophils by chemiluminescence. In students with a high level of physical activity, the content of T and B lymphocytes in the blood was significantly increased compared to similar indicators of the group with a low level of physical activity and the group of students who did not participate in sports. The concentration of class G immunoglobulin in the blood serum of students with a high level of physical activity significantly exceeded the corresponding values in students with an average level and students not engaged in sports. The highest concentration of class M immunoglobulin was observed in students with high levels of physical activity. Phagocytic activity and phagocytic count in individuals with high levels of physical activity and neutrophils were significantly higher than those of students with medium and low levels of physical activity. The rates of spontaneous and induced chemiluminescence in the groups with high and medium levels of physical activity were significantly higher than in students with low levels. The studies carried out indicate the positive effect of regular training physical activity on the factors of humoral and cellular links of immunity in students in the conditions of the educational environment of a higher educational institution.

Malnutrition drives infection susceptibility and dysregulated myelopoiesis that persists after refeeding intervention.

Undernutrition is one of the largest persistent global health crises, with nearly 1 billion people facing severe food insecurity. Infectious disease represents the main underlying cause of morbidity and mortality for malnourished individuals, with infection during malnutrition representing the leading cause of childhood mortality worldwide. In the face of this complex challenge, simple refeeding protocols have remained the primary treatment strategy. Although an association between undernutrition and infection susceptibility has been appreciated for over a century, the underlying mechanisms remain poorly understood and the extent to which refeeding intervention is sufficient to reverse nutritionally acquired immunodeficiency is unclear. Here we investigate how malnutrition leads to immune dysfunction and the ability of refeeding to repair it. We find that chronic malnutrition severely impairs the ability of animals to control a sub-lethal bacterial infection. Malnourished animals exhibit blunted immune cell expansion, impaired immune function, and accelerated contraction prior to pathogen clearance. While this defect is global, we find that myelopoiesis is uniquely impacted, resulting in in reduced neutrophil and monocyte numbers prior to and post-infection. Upon refeeding, we observe that animals recover body mass, size, cellularity across all major immune organs, the capacity to undergo normal immune cell expansion in response to infection, and a restoration in T cell responses. Despite this broad improvement, refed animals remain susceptible to bacterial infection, uncoupling global lymphoid atrophy from immunodeficiency. Mechanistically, we find peripheral neutrophil and monocyte numbers fail to fully recover and refed animals are unable to undergo normal emergency myelopoiesis. Altogether, this work identifies a novel cellular link between prior nutritional state and immunocompetency, highlighting dysregulated myelopoiesis as a major driver. We believe these findings illustrate how exposure to food scarcity is an immunologic variable, even post-recovery, which should be accounted for in patient medical history and current global public health policy.

Role of the circadian nuclear receptor REV-ERBα in dorsal raphe serotonin synthesis in mood regulation

Affective disorders are frequently associated with disrupted circadian rhythms. The existence of rhythmic secretion of central serotonin (5-hydroxytryptamine, 5-HT) pattern has been reported; however, the functional mechanism underlying the circadian control of 5-HTergic mood regulation remains largely unknown. Here, we investigate the role of the circadian nuclear receptor REV-ERBα in regulating tryptophan hydroxylase 2 (Tph2), the rate-limiting enzyme of 5-HT synthesis. We demonstrate that the REV-ERBα expressed in dorsal raphe (DR) 5-HTergic neurons functionally competes with PET-1—a nuclear activator crucial for 5-HTergic neuron development. In mice, genetic ablation of DR 5-HTergic REV-ERBα increases Tph2 expression, leading to elevated DR 5-HT levels and reduced depression-like behaviors at dusk. Further, pharmacological manipulation of the mice DR REV-ERBα activity increases DR 5-HT levels and affects despair-related behaviors. Our findings provide valuable insights into the molecular and cellular link between the circadian rhythm and the mood-controlling DR 5-HTergic systems.

Renal IL-23-Dependent Type 3 Innate Lymphoid Cells Link Crystal-induced Intrarenal Inflammasome Activation with Kidney Fibrosis.

Chronic inflammasome activation in mononuclear phagocytes (MNPs) promotes fibrosis in various tissues, including the kidney. The cellular and molecular links between the inflammasome and fibrosis are unclear. To address this question, we fed mice lacking various immunological mediators an adenine-enriched diet, which causes crystal precipitation in renal tubules, crystal-induced inflammasome activation, and renal fibrosis. We found that kidney fibrosis depended on an intrarenal inflammasome-dependent type 3 immune response driven by its signature transcription factor Rorc (retinoic acid receptor-related orphan receptor C gene), which was partially carried out by type 3 innate lymphoid cells (ILC3s). The role of ILCs in the kidney is less well known than in other organs, especially that of ILC3. In this article, we describe that depletion of ILCs or genetic deficiency for Rorc attenuated kidney inflammation and fibrosis. Among the inflammasome-derived cytokines, only IL-1β expanded ILC3 and promoted fibrosis, whereas IL-18 caused differentiation of NKp46+ ILC3. Deficiency of the type 3 maintenance cytokine, IL-23, was more protective than IL-1β inhibition, which may be explained by the downregulation of the IL-1R, but not of the IL-23R, by ILC3 early in the disease, allowing persistent sensing of IL-23. Mechanistically, ILC3s colocalized with renal MNPs invivo as shown by multiepitope-ligand cartography. Cell culture experiments indicated that renal ILC3s caused renal MNPs to increase TGF-β production that stimulated fibroblasts to produce collagen. We conclude that ILC3s link inflammasome activation with kidney inflammation and fibrosis and are regulated by IL-1β and IL-23.

Determination of the Coefficients "a" and "b" of the K-R Relationship for Accurate Measurement of Water Quantity Using Cellular Links in Burkina Faso

Determination of the Coefficients "a" and "b" of the K-R Relationship for Accurate Measurement of Water Quantity Using Cellular Links in Burkina Faso

CHARACTERISTICS OF IMMUNOREACTIVITY IN THE RAT UNDER CONDITIONS OF TOXIC INJURY WITH ACETAMINOPHEN

The aim of this work was to to determine the integral leukocyte indices in animals with toxic damage by acetaminophen on the background of protein deficiency. The study was conducted on 4 groups of animals: Group I - control animals (K); II – rats kept on a low-protein diet (LPD); ІІІ – animals with acetaminophen-induced liver injury receiving complete ration (AII); IV – animals with acetaminophen-induced liver injury that were previously maintained on semi-synthetic low-protein ration (LPD/AII). Preparation of blood smears, their fixation and staining was carried out by the generally accepted method. The ratio of different types of leukocytes in stained blood smears was calculated using a standard method using a leukocyte counter and a microscope (eyepiece × 10, objective × 100). Standard formulas were used to calculate integral hematological indices. It was established that the supply of protein in the diet is critical for the functioning of the immune system under conditions of acetaminophen intoxication, since under these conditions there is a change in leukocyte indices, in particular, the index of immunoreactivity, the index of leukocyte shift, the index of the ratio of neutrophils and lymphocytes, the index of the reactive response of neutrophils, which indicates the intensification of inflammatory processes in the body and the formation of defects in the cellular link of immunity, disruption of the mechanisms of the specific immune response and the formation of a state of endotoxicosis. The obtained results can be used to develop approaches to the early diagnosis of impaired immunoreactivity in animals with toxic damage by acetaminophen against the background of dietary protein deficiency, while the studied integral hematological indicators can be used as additional early diagnostic markers of impaired immunoreactivity and endotoxicosis. Key words: acetaminophen, dietary protein deficiency, leukocytes, immunoreactivity indices

Neuromolecular mechanisms related to reflex behaviour in Aplysia are affected by ocean acidification.

While ocean acidification (OA) impacts the behaviour of marine organisms, the complexity of neurosystems makes linking behavioural impairments to environmental change difficult. Using a simple model, we exposed Aplysia to ambient or elevated CO2 conditions (approx. 1500 µatm) and tested how OA affected the neuromolecular response of the pleural-pedal ganglia and caused tail withdrawal reflex (TWR) impairment. Under OA, Aplysia relax their tails faster with increased sensorin-A expression, an inhibitor of mechanosensory neurons. We further investigate how OA affects habituation training output, which produced a 'sensitization-like' behaviour and affected vesicle transport and stress response gene expression, revealing an influence of OA on learning. Finally, gabazine did not restore normal behaviour and elicited little molecular response with OA, instead, vesicular transport and cellular signalling link other neurotransmitter processes with TWR impairment. Our study shows the effects of OA on neurological tissue parts that control for behaviour.

Study on covert rate in the D2D networks with multiple non-colluding wardens

This paper investigates the covert communication of cellular link in the device-to-device (D2D)-enabled underlaying cellular network, including a base station, a cellular user, a D2D pair, and multiple non-colluding wardens. To conduct covert communication between the base station and the cellular user without being detected by the wardens, the underlaid D2D pair transmits with a random power to add uncertainty to wardens. We first model the detection of multiple non-colluding wardens, and the average minimum detection error probability of the worst case is derived. To measure the covert performance of the cellular link, the average covert rate of the cellular link and the outage probability of the D2D link are explored. Then, we formulate an optimization problem of maximizing the average covert rate under the constraint of the average minimum detection error probability, and an optimization algorithm is designed to solve the optimization problem to identify the optimal transmit power of the D2D pair. Last, the extensive numerical results are presented to show the impacts of network parameters on the covert performance, which indicates that although D2D communication causes interference to the cellular link, it can also help achieve covert communication by carefully designing its maximum transmit power.

CORRELATIONS OF CARBOHYDRATE, LIPID METABOLISM AND THE IMMUNE SYSTEM INDICATORS IN ISCHEMIC HEART DISEASE AGAINST THE BACKGROUND OF THE METABOLIC SYNDROME

Introduction. Coronary heart disease (CHD) is the most common form of heart disease, which is one of the leading causes of death in the world.A combination of several factors has a special effect on the course of coronary heart disease, which significantly worsens the unfavorable prognosis.
 Purpose: to determine the correlations of the studied indicators in patients with coronary artery disease against the background of metabolic syndrome.
 Research methods. 60 patients had verified coronary heart disease without metabolic syndrome - group 1, the other 60 patients had verified coronary heart disease (CHD) complicated by metabolic syndrome (MS) - group 2. In order to identify correlations, the linear correlation coefficient |r|between all studied indicators.
 Results and discussion. In both groups of patients, the main interactions were found between glucose content and other indicators, as well as numerous correlations of lipid metabolism indicators with other studied indicators.In the group of patients with coronary artery disease, strong positive correlations were found between the creatinine clearance index and hemoglobin concentration; hematocrit; content of erythrocytes; a strong negative relationship with the age of patients. In the group of patients with MS, strong positive correlations were found between creatinine clearance and NT-proBNP, ST 2, and pro-inflammatory cytokines.
 Conclusion. When analyzing the obtained results, numerous correlations of lipid metabolism indicators with other studied indicators were found.In coronary heart disease against the background of metabolic syndrome, a direct pathogenetic connection of hyperglycemia with pro-inflammatory interleukin, which activates the cellular link of non-specific immunity (phagocytosis), is revealed. The depressing effect of hyperglycemia on other links of immune defense and indicators of lipid metabolism is also revealed.ST 2 positively correlates with NT-proBNP indicators in patients with coronary artery disease on the background of MS, which indicates the presence of ischemic and metabolic disorders in these patients.

Metapneumovirus infection in children in modern conditions: clinical and immunological parallels

Aim. The study of metapneumovirus infection clinical and immunological features in children of different ages. Patients and methods. An analysis of 22 patients with mono-metapneumovirus infection is presented. There were 7 (31.8%) children under the age of 1 year, 8 (36.4%) — 1—3 years old, 7 (31.8%) — 4—7 years old. Diagnosis of metapneumovirus infection was based on clinical data and on PCR analysis of nasopharyngeal mucus. Immunological studies in 10 patients included immunophenotype of patient's blood lymphocytes and analysis of the interferon system. Results. Among children under the age of 1 year 71.4 ± 17.1% were diagnosed with obstructive bronchitis and 28.6 ± 17.1% had pneumonia. In patients aged 1—3 years pneumonia was observed more often (55.6 ± 17.6%), obstructive bronchitis — less often (33.3 ± 16.7%), and in 11.1 ± 11.1% bronchitis occurred without symptoms of bronchial obstruction. In children aged 4—7 years only the upper respiratory tract was affected in 14.3 ± 13.2% of cases, 57.1 ± 18.7% developed bronchitis and 28.6 ± 17.1% — pneumonia. The immune system state was characterized by a low content of T-helpers (CD3 + CD4 + ) and NK-cells (CD3-CD16 + CD56 + ) detected in 7 (70%) and 5 (50%) patients respectively. IFNγ production was reduced in 70% of children and IFNα in 80%. Conclusion. Metapneumovirus infection in children in modern conditions is characterized by the frequent development of inflammatory changes in the bronchopulmonary system in the early stages of the disease. The disease severity was due to both manifestations of respiratory failure and severe symptoms of intoxication. Immunological studies revealed changes in the cellular link and the interferon system in all age groups.

Discovery and Characterization of Fluopipamine, a Putative Cellulose Synthase 1 Antagonist within Arabidopsis.

Herbicide-resistant weeds are increasingly a problem in crop fields when exposed to similar chemistry over time. To avoid future yield losses, identifying herbicidal chemistry needs to be accelerated. We screened 50,000 small molecules using a liquid-handling robot and light microscopy focusing on pre-emergent herbicides in the family of cellulose biosynthesis inhibitors. Through phenotypic, chemical, genetic, and in silico methods we uncovered 6-{[4-(2-fluorophenyl)-1-piperazinyl]methyl}-N-(2-methoxy-5-methylphenyl)-1,3,5-triazine-2,4-diamine (fluopipamine). Symptomologies support fluopipamine as a putative antagonist of cellulose synthase enzyme 1 (CESA1) from Arabidopsis (Arabidopsis thaliana). Ectopic lignification, inhibition of etiolation, phenotypes including loss of anisotropic cellular expansion, swollen roots, and live cell imaging link fluopipamine to cellulose biosynthesis inhibition. Radiolabeled glucose incorporation of cellulose decreased in short-duration experiments when seedlings were incubated in fluopipamine. To elucidate the mechanism, ethylmethanesulfonate mutagenized M2 seedlings were screened for fluopipamine resistance. Two loci of genetic resistance were linked to CESA1. In silico docking of fluopipamine, quinoxyphen, and flupoxam against various CESA1 mutations suggests that an alternative binding site at the interface between CESA proteins is necessary to preserve cellulose polymerization in compound presence. These data uncovered potential fundamental mechanisms of cellulose biosynthesis in plants along with feasible leads for herbicidal uses.

THE STATE OF THE IMMUNE SYSTEM OF HORSES IN CONDITIONS OF STRESS

The study assessed the impact of adverse conditions of feeding and keeping horses on the state of their non-specific resistance. Morphological indicators of blood (hemoglobin content, number of erythrocytes and leukocytes), as well as indicators of humoral (BASC, LASC) and cellular link of innate immunity (phagocytic activity of leukocytes) were used. During the experiment, the horses had a satisfactory general clinical condition, and the main physiological indicators (body temperature, arterial pulse frequency, number of respiratory movements) were within the age norm. It is important to note that there was no significant difference between these parameters in animals at different time periods, which indicated a stable physiological state of the horses at the beginning and at the end of the experiment. The results of the study showed that long-term stress can cause changes in the hematological and biochemical parameters of horses. For example, the level of hemoglobin in clinically healthy horses was 136±2.2 g/l, but after exposure to stress factors it decreased to 110±1.8 g/l (р<0.001). At the stage of adaptation, the hemoglobin level increased to 124±2.6 g/l (р<0.01) and almost reached the values of clinically healthy horses (132±3.2 g/l) at rest. The number of erythrocytes in clinically healthy horses was 8.8±0.1 T/l. Under stress, this indicator increased to 9.8±0.2 T/l (р<0.01), but decreased to 9.6±0.2 T/l (р<0.05) at the stage of adaptation and reached the lowest level at rest — 8.6±0.1 T/l. A decrease in the number of leukocytes under the influence of stress has been confirmed by our research. In clinically healthy horses, the number of leukocytes was 6.7±0.3 G/l, while under stress this indicator decreased to 5.3±0.2 g/l (p<0.001). At the stage of adaptation, the number of leukocytes increased to 5.5±0.3 g/l (р<0.01) and was 6.2±0.3 G/l at rest. Stress also affected the indicators of non-specific resistance. In clinically healthy horses, the level of BASC was 85±1.8%, but under stress this indicator decreased to 70±2.1% (р<0.001). At the stage of adaptation, BASK increased to 75±1.1% (р<0.01), and at rest it was 82±1.7%. The level of LASK in clinically healthy horses was 35±0.2%, but under stress this indicator decreased to 28±0.4% (р<0.001). At the stage of adaptation, LASK increased to 30±0.2% (p<0.001) and reached 36±0.5% at rest. The phagocytic activity of leukocytes in clinically healthy horses was 60±1.5%, but under stress this indicator decreased up to 50±1.1% (р<0.001). At the stage of adaptation, phagocytic activity increased to 55±0.5% (р<0.01) and was 63±0.9% (р<0.05) at rest. Thus, the results of our study confirm that stress negatively affects the hematological and biochemical parameters of horses, as well as their non-specific resistance.

PATHOGENESIS OF IMMUNE DYSFUNCTION IN THE SETTING OF METABOLIK SYNDROME IN CORONARY HEAT DISEASE. QUALIFYING SCENTIFYING WORK ON THE RIGHTS OF THE MANUSCRIPT

PATHOGENESIS OF IMMUNE DYSFUNCTION IN THE SETTING OF METABOLIK SYNDROME IN CORONARY HEAT DISEASE. QUALIFYING SCENTIFYING WORK ON THE RIGHTS OF THE MANUSCRIPT

The Effect of Retinol Acetate on Liver Fibrosis Depends on the Temporal Features of the Development of Pathology

The effect of vitamin A on the manifestations of liver fibrosis is controversial and establishing the causes of its multidirectional influence is an urgent problem. In the work, the functional characteristics of the liver with Cu-induced fibrosis were determined after the restoration of vitamin A to the control level at the F0/F1 stage. In animals with liver fibrosis, classical indicators of physiology, functional activity of the liver, histological, and hematological characteristics were determined; the content of calcium and ROS was determined in bone marrow cells. It was shown that in the liver with Cu-induced fibrosis, the restoration of vitamin A content to control values after per os injections of a retinol acetate solution at a dose of 0.10mg (300 IU)/100g of body weight in the early stages of this pathology development (Fо/F1) was accompanied by: a decrease in the number of immunocompetent cells in the bloodstream to control values; normalization of the amount of calcium ions and ROS in bone marrow cells; restoration to the control level of activity of alkaline phosphatase; an increase in the number of binuclear hepatocytes; and restoration of the dynamics of body weight growth in experimental animals, even against the background of the ongoing action of the hepatotoxic factor. We came to the conclusion that the multidirectional action of vitamin A, which occurs in liver fibrosis, depends not only on the concentration of vitamin A in the liverbut also on temporal characteristics of cellular and metabolic links involved in the adaptive response formation. It was suggested that knowledge of the initial temporal metabolic characteristics and the amount of vitamin A in the liver, taking into account the stages of fibrosis development, can be an effective way to restore the altered homeostatic parameters of the body.

Unraveling the complexities of fibrosis and ductular reaction in liver disease: pathogenesis, mechanisms, and therapeutic insights.

Ductular reaction and fibrosis are hallmarks of many liver diseases including primary sclerosing cholangitis, primary biliary cholangitis, biliary atresia, alcoholic liver disease, and metabolic dysfunction-associated steatotic liver disease/metabolic dysfunction-associated steatohepatitis. Liver fibrosis is the accumulation of extracellular matrix often caused by excess collagen deposition by myofibroblasts. Ductular reaction is the proliferation of bile ducts (which are composed of cholangiocytes) during liver injury. Many other cells including hepatic stellate cells, hepatocytes, hepatic progenitor cells, mesenchymal stem cells, and immune cells contribute to ductular reaction and fibrosis by either directly or indirectly interacting with myofibroblasts and cholangiocytes. This review summarizes the recent findings in cellular links between ductular reaction and fibrosis in numerous liver diseases.

Immunomodulatory leptin receptor+ sympathetic perineurial barrier cells protect against obesity by facilitating brown adipose tissue thermogenesis

Adipose tissues (ATs) are innervated by sympathetic nerves, which drive reduction of fat mass via lipolysis and thermogenesis. Here, we report a population of immunomodulatory leptin receptor-positive (LepR+) sympathetic perineurial barrier cells (SPCs) present in mice and humans, which uniquely co-express Lepr and interleukin-33 (Il33) and ensheath AT sympathetic axon bundles. Brown ATs (BATs) of mice lacking IL-33 in SPCs (SPCΔIl33) had fewer regulatory T (Treg) cells and eosinophils, resulting in increased BAT inflammation. SPCΔIl33 mice were more susceptible to diet-induced obesity, independently of food intake. Furthermore, SPCΔIl33 mice had impaired adaptive thermogenesis and were unresponsive to leptin-induced rescue of metabolic adaptation. We therefore identify LepR+ SPCs as a source of IL-33, which orchestrate an anti-inflammatory BAT environment, preserving sympathetic-mediated thermogenesis and body weight homeostasis. LepR+IL-33+ SPCs provide a cellular link between leptin and immune regulation of body weight, unifying neuroendocrinology and immunometabolism as previously disconnected fields of obesity research.

The state of cellular immunity link and steroid hormones in bitches under different conditions of the reproductive system

The purpose of the conducted study was to establish the correlation between indicators of the cellular immunity link and the concentration of steroid hormones in bitches under different conditions of the reproductive system. Seventeen crossbred bitches aged from 2 to 5 years were involved in the experiment. They were divided into three groups depending on the state of the reproductive system: anestrus, sexual cycle, and pyometra. The following immunophysiological indicators were determined in blood plasma: the absolute number of leukocytes, lymphocytes, and their immunoregulatory subpopulations, and the phagocytic activity of neutrophils. The content of progesterone, estradiol, and cortisol was determined in serum. According to the results of the research, it was established that the absolute number of neutrophils, as the most reactogenic cells of the innate link of cellular immunity, was 0.51 G/L higher in the group of animals with pyometra than in the group of animals during the sexual cycle, and by 0.84 G/L in bitches in conditions of anestrus. The absolute number of phagocytic active neutrophils in conditions of pyometra was 2.32 ± 0.58 G/L (Р < 0.001). However, as a percentage of the absolute number of neutrophils, this indicator was 66 %. During the sexual cycle, the absolute number of neutrophils capable of phagocytosis was 2.33 ± 0.51 G/L, which is 78 % of the absolute number of all neutrophilic leukocytes. The indicator of the absolute number of lymphocytes was reliably (P < 0.05) lower in the group of bitches with pyometra – 1.48 ± 0.35 G/L, which is 0.92 G/L less compared to the group of animals in the anestrous period. Analysis of the absolute number of monocytes showed that this indicator was the same in bitches during the pyometra and anestrous periods and was lower by 0,07 G/L during the sexual cycle. The absolute number of B-lymphocytes, as a humoral link of adaptive immunity, in bitches in conditions of the anestrous and estrous period was the same and amounted to 0.30 G/L. In the group of bitches with pyometra, a reliable decrease of this indicator by 33 % was established (Р < 0.05). The population of natural killer (NK) lymphocytes was also the lowest in bitches with pyometra, almost twice as compared to animals during the sexual cycle. Conducted research on determining the absolute quantitative indicators of the cellular immunity link showed their dependence on the functional state of the reproductive system. It was established that the absolute number of neutrophils in pyometra was higher than in animals in anestrus. However, at the same time, their relative number capable of phagocytosis was the lowest. In conditions of pyometra, the lowest number of lymphocytes and their main subpopulations were observed.