Development Of Allergic Inflammation Research Articles

Natural killer cells contribute to ‘hot’ tumor regression in the allergic inflammatory environment

Systemic immune status influences the elimination of tumor cells. However, it remains unclear how chronic inflammation in allergic diseases affects the tumor microenvironment and tumorigenesis. To investigate tumor progression in a state of heightened allergic inflammation, we established a mouse model of allergic inflammation. We used house dust mite extract to induce a hyper-reactive systemic immune response. Additionally, we subcutaneously inoculated two types of cancer cells (CT26 and 4T1 tumors). We conducted immune profiling of the ex-vivo tumor mass using multicolor flow cytometry staining and performed dynamic analysis of peripheral cytokines to explore the significant relationship between the development of allergic inflammation and tumorigenesis. We found that mice in a state of allergic inflammation were more susceptible to developing tumors. Interestingly, the growth of T cell-inflamed was inhibited in the allergic state, while growth of non-T cell-inflamed was promoted. Further research revealed that natural killer (NK) cells with enhanced tumor-killing or immune-regulating abilities were more active in “ hot ” tumors. Inhibiting NK cell activity can partially alleviate the impact of allergic inflammation on tumor growth. In summary, our results suggest that NK cells play significant role in suppressing tumor growth in an allergic inflammation mouse model. This phenomenon seems to be closely linked to both the inherent characteristics of the tumor and its interaction with the immune system. The innate immune system can be mobilized to synergize with the adaptive immune system to inhibit tumor growth, which opens a new way for a tumor immunotherapy.

How Do Pollen Allergens Sensitize?

Plant pollen is one of the main sources of allergens causing allergic diseases such as allergic rhinitis and asthma. Several allergens in plant pollen are panallergens which are also present in other allergen sources. As a result, sensitized individuals may also experience food allergies. The mechanism of sensitization and development of allergic inflammation is a consequence of the interaction of allergens with a large number of molecular factors that often are acting in a complex with other compounds, for example low-molecular-mass ligands, which contribute to the induction a type 2-driven response of immune system. In this review, special attention is paid not only to properties of allergens but also to an important role of their interaction with lipids and other hydrophobic molecules in pollen sensitization. The reactions of epithelial cells lining the nasal and bronchial mucosa and of other immunocompetent cells will also be considered, in particular the mechanisms of the activation of B and T lymphocytes and the formation of allergen-specific antibody responses.

Airway epithelial STAT3 inhibits allergic inflammation via upregulation of stearoyl-CoA desaturase 1

BackgroundAirway epithelial cells (AECs) play a crucial role in the induction and development of allergic inflammation through the development and activation of immune cells, including Th2 cells and ILC2s. Recent studies have revealed that STAT3 expressed in epithelial cells protects against pathogens and maintains homeostasis in the intestine. However, the roles of STAT3 in airway epithelium are poorly understood. Therefore, we sought to elucidate the roles of airway epithelial STAT3 in allergic airway inflammation. MethodsAllergic airway inflammation was induced by intratracheal administration of house dust mite (HDM) extract in doxycycline-induced AEC-specific STAT3-deficient (STAT3-cKO) mice and their genetic control (STAT3-WT) mice. Airway inflammation was evaluated by flow cytometric analysis of bronchoalveolar lavage fluid cells and histological analysis of the lung. Purified airway epithelial cells were analyzed by quantitative PCR and RNA-sequencing (RNA-seq). ResultsHDM-induced airway inflammation was exacerbated in STAT3-cKO mice compared with STAT3-WT mice. RNA-seq analyses revealed that Scd1, coding stearoyl-CoA desaturase 1, was most significantly upregulated in HDM-treated STAT3-WT mice compared to HDM-treated STAT3-cKO mice. Notably, the administration of an SCD1 inhibitor exacerbated HDM-induced airway inflammation. AECs of HDM-treated STAT3-cKO mice and those of HDM-treated SCD1 inhibitor-injected mice shared 45 differentially expressed genes (DEGs). Gene enrichment analysis of the DEGs revealed that the enriched ontology clusters included fatty acid biosynthetic process and regulation of lipid biosynthetic process, suggesting the involvement of the STAT3-SCD1-lipid metabolism axis in suppressing allergic inflammation. ConclusionsSTAT3 is crucial for suppressing HDM-induced allergic airway inflammation, possibly inducing SCD1 expression in AECs.

Роль однонуклеотидних варіантів гена тимічного стромального лімфопоетину у прогнозуванні моно- та поліорганного ураження в дітей, хворих на атопічні захворювання

Atopic diseases (AtD) in children — atoic dermamatitis (AD), allergic rhinitis / rhinoconjunctivits (AR/ARC), bronchial asthma (BA) — remain an actual problem in modern pediatrics. Thymic stromal lymphopoietin (TSLP) is one of the key agents involved in the development of allergic inflammation in the barrier organs — the skin and mucous membranes of the airways. The role of single nucleotide variants (SNVs) of the TSLP gene in the development of monoorganic or polyorganic lesions within AD in children has been insufficiently studied and needs to be elucidated. Purpose — to determine the role of SNV rs11466749 of TSLP gene in the risk of developing mono- and polyorganic phenotypes of AtD in children (AD, AR/ARC and/or asthma). Materials and methods. The study recruited 293 children into the main and 105 — into control groups aged 3 to 18 years. Patients of the main group had been clinically diagnosed with of AD, AR/ARC and BA isolated or in different combinations. Patients in the control group were clinically excluded the diagnosis of AD and diagnosed with diseases of the digestive system (chronic gastritis, chronic duodenitis, peptic ulcer disease, functional disorders of the biliary system). For genotyping of the variants A/A, A/G, G/G SNV rs11466749 of the TSLP gene, buccal swab of the oral mucosa was performed in patients of the main and control groups. Cluster analysis was used, for which all patients of the main group were divided into 6 clusters: with monoorganic lesions: № 1 — AD (58 patients), № 2 — AR/ARC (71 patient), № 3 — BA (26 patients); with polyorganic lesions: № 4 — AD+AR/ARC (43 patients); № 5 — BA+AR/ARC (23 patients); № 6 — AD+AR/ARC+BA (72 patients). Comparative analysis between clusters was performed for the genotype variants A/A, A/G, G/G SNV rs11466749 TSLP gene. The criterion of statistical significance was determined as p<0.05. Results. The A/A genotype SNV rs11466749 of TSLP gene is the most common variant in patients with AtD and significantly increases the risk of their development by 1.61 fold. Variant A/G SNV rs11466749 of TSLP gene is antagonistic to A / A and is significantly more common in patients without AtD and decreases the risk of their development by 1.69 times. The A/A genotype rs11466749 of TSLP gene is the most common genotype in both monoorganic and polyorganic lesions in children with AtD. Its highest incidence was recorded in the phenotype of complete polyorganic lesion — AD+AR/ARC+BA. Variant A/G SNV rs11466749 of TSLP gene significantly increases the risk of developing the monoorganic phenotype of BA by 4.93 times and polyorganic BA+AR/ARC by 3.89 fold related to the complete polyorganic phenotype AD+AR/ARC+BA. Variant A/G SNV rs11466749 of TSLP gene significantly decreases the risk of developing the complete poliorgan phenotype AD+AR/ARC+BA by 3.23 and 4.17 fold related to the monоorganic phenotype of AD and polyorganic AD+AR/ARC respectively. Variant A/G SNV rs11466749 of TSLP gene with a tendency to statistical significance increases by 3.44 fold the risk of developing the monoorganic phenotype of AR/ARC related to the complete polyorganic phenotype AD+AR/ARC+BA. Variant A/A SNV rs11466749 of TSLP gene with a tendency to significance increases the risk of developing the complete polyorganic phenotype AD+AR/ARC+BA by 2.71 and 2.64 fold related to the monоorganic phenotype of AD and polyorganic AD+AR/ARC respectively. Variant A/A SNV rs11466749 of TSLP gene with a tendency to significance decreases by 3.03 fold the risk of developing the monoorganic phenotype of AD related to the complete polyorganic phenotype AD+AR/ARC+BA. Conclusions. Genotypic variants of the rs11466749 of TSLP gene play antagonistic roles in children: A/A significantly increases and A/G significantly decreases the risk of developing a common AtD phenotype. Determination of genotype variants A/A, A/G and G/G SNV rs11466749 of TSLP gene in children allows to personalize and increase the efficiency of predictive AtD diagnostics in children with mono- and polyorganic lesion phenotypes. The research was carried out in accordance with the principles of the Helsinki declaration. The study protocol was approved by the Local ethics committee of all participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: atopic diseases, children, single nucleotide variants, thymic stromal lymphopoetin, monoorganic lesions, polyorganic lesions.

Dynamics of quantitative changes of diffuse lymphoid tissue cells of bronchi and lungs of guinea pigs sensitized with ovalbumin

Background. There is a progressive increase of respiratory allergic diseases nowadays in the world, made it necessary to study the participation of the components of the immune system in these processes. From the point of view of modern aspects about the organs of the immune system, interesting are the patterns of morphogenesis and function of bronchus associated lymphoid tissue, occupied a special place in the immunological protection of the body due to the large area of contact with various antigens. Morphogenesis and reactive changes in the local immunity in respiratory system in conditions of allergic inflammation remain urgent issue of modern morphology. Objective. To study the changes in diffuse lymphoid tissue of bronchi and lungs of guinea pigs sensitized with ovalbumin. Methods. We have studied the lung of 48 guinea pigs, using histological, immunohistochemical, morphometric, statistical methods, under conditions of experimental ovalbumin-induced allergic inflammation, assessed the average number of lymphocytes, macrophages and plasma cells in the diffuse lymphoid tissue. Results. The average number of lymphocytes in diffuse lymphoid tissue of bronchi and lungs increased from the 23rd day of observation and remained at a high level until the end of the experiment, the maximum was during the early period of the development of allergic inflammation, the increasing coefficient was 4.7. The average number of plasma cells also acquired maximum elevation in the early period of allergic process, the increasing coefficient was 2.0. The most significant average number of macrophages was on the 23rd day of observation with same increasing coefficient. Among all types of immunocompetent cells of diffuse lymphoid tissue in bronchi and lungs, T-lymphocytes prevailed during the experiment elevated almost by 5 times. Conclusions. In the early period of development of experimental ovalbumin-induced allergic inflammation, the specific resistance of the respiratory system manifests itself in the form of activation of local links of cellular and humoral adaptive immunity, as evidenced by the dynamics of changes in the average number of lymphocytes (the maximum increasing coefficient 4.7 in the 1st experimental group), macrophages and plasma cells (maximum increasing coefficient 2.0 in the 1st experimental group) of diffuse lymphoid tissue of bronchi and lungs of guinea pigs.

The Role of Secreted Frizzled-related Protein-1 in Allergic Asthma.

Although allergic asthma is a highly prevalent chronic inflammatory condition, the underlying pathogenesis driving T-helper cell type 2 inflammation is not well understood. Wnt/β-catenin signaling has been implicated, but the influence of individual members of the pathway is not clear. We hypothesized that SFRP-1 (secreted frizzled-related protein-1), a Wnt signaling modulator, plays an important role in the development of allergic inflammation in asthma. Using an invivo house dust mite asthma model, SFRP-1-/- mice were sensitized, and their BAL fluid was collected to evaluate airway inflammation. SFRP-1-/- mice exhibited less inflammation with reduced cellular infiltration and concentration of IL-5 in bronchoalveolar lavage fluid compared with wild-type (WT) mice. Similar findings were observed in WT mice treated with SFRP-1 inhibitor, WAY316606. Alveolar macrophages from sensitized SFRP-1-/- mice demonstrated reduced alternative polarization compared with WT, indicating that macrophages could mediate the alteration in inflammation seen in these mice. These findings suggest that SFRP-1 is an important potentiator of asthmatic airway inflammation.

MORPHOLOGICAL CHARACTERISTICS OF GUINEA PIGS BRONCHUS ASSOCIATED LYMPHOID TISSUE IN THE DYNAMICS OF EXPERIMENTAL OVALBUMIN-INDUCED ALLERGIC INFLAMMATION

The actual problem of modern medicine is the reaction of Bronchus associated lymphoid tissue in airways chronic allergic diseases, because the full functioning of the respiratory system depends on the state of its local immune system.
 The aim – to study morphological changes in Bronchus associated lymphoid tissue of guinea pigs in the dynamics of experimental ovalbumin-induced allergic inflammation.
 Material and Methods. We have studied the lung of 48 guinea pigs, using histological and morphometric methods, under conditions of experimental ovalbumin-induced allergic inflammation. To assess the structural and functional rearrangement of pulmonary lymphoid nodules, their diameter and number were determined.
 Results. We have shown that sensitization and allergization with ovalbumin leads to a significant structural and functional rearrangement of Bronchus associated lymphoid tissue of guinea pigs in the form of the elevation in their number and diameter. We found more pronounced morphological changes in the late period of development of allergic inflammation in peribronchial lymphoid nodules, confirmed by the maximum magnification factor – 2.6 (p*/**<0.001) of the diameter of peribronchial lymphoid nodules in the 4th experimental group compared to the control.
 Conclusions. Sensitization and inhalation with ovalbumin leads to structural reorganization of Bronchus associated lymphoid tissue of guinea pigs in the form of the elevation in their number and diameter, had the unidirectional staged character depending on localization of lymphoid nodules and the duration of the experiment and claimed proliferative changes in the cellular adaptive link of local lung immunity of guinea pigs in late period of allergic inflammatory process.

Reaction of eosinophilic granulocytes of guinea pigs airways to the experimental allergic inflammation according to the morphometric study

Background. After creating an animal model of experimental airways allergic inflammation using ovalbumin, scientists mainly studied the reaction of the cellular and humoral links of the acquired specific immunity. At the same time, it is known that the development of allergic inflammation of the airways to the effect of the environmental chemoattractants is primarily the result of the local innate immune system response. Pulmonary neuroendocrine cells of the airway epithelium with the help of neuropeptides activate the secretion of IL-5 and IL-13 by type 2 innate lymphoid cells IL-5 determines the eosinophilic inflammation. The question of the reaction of the components of innate immunity of the respiratory tract to the allergic inflammation in most aspects remains open. open. Objective. The purpose of the current study was to define the reaction of eosinophilic granulocytes in guinea pigs lungs as an important component of the innate immunity of the respiratory tract to experimental ovalbumin-induced allergic inflammation according to the data of a morphometric study. Methods. Histological, morphometric, statistical methods were used to study the topographic features and the number of eosinophils in the lungs of male 48 guinea pigs on the 23rd, 30th, 36th and 44th days after initiation of the experimental ovalbumin-induced allergic airway inflammation. Results. Our study demonstrates a significant reaction occurs on the part of the cellular link of innate immunity, which consists in the activation of eosinophils, in the experimental model of ovalbumin-induced airways allergic inflammation. The most significant changes were observed in the distal parts of the intrapulmonary airways and in the structures of the pulmonary acinus in the early period of the development of the inflammatory process (23rd and 30th days after the start of the experiment). The late (36th and 44th days after the start of the experiment) period of the development of an allergic inflammatory process in the lungs is accompanied by a gradual decrease in the activity of eosinophilic inflammation. At the same time, the quantitative indicators remain statistically significantly higher in the intact and control groups, which indicates the continuation of allergic inflammation in the absence of the action of the allergen and is a manifestation of the violation of the recovery and adaptation processes in the local immune system of the lung. Conclusion. After ovalbumin-sensitization and aeroallergization eosinophilic inflammation develops in the lungs of a guinea pig, as a result of the reaction of the innate immunity to the action of an allergen. Actively and first of all, allergic eosinophilic inflammation develops in the distal airways (terminal bronchioles) and in the connective tissue stroma of the pulmonary acinus.

Клінічні прояви гастроінтестинальної форми харчової алергії у дітей і підходи до її діагностики

Гастроінтестинальна харчова алергія обумовлена розвитком алергічного запалення в слизовій оболонці шлунково-кишкового тракту, механізмами якого є як імуноглобулін E (IgE)-опосередковані (оральний алергічний синдром, негайна гастроінтестинальна гіперчутливість.), так і не-IgE-опосередковані (білок-індукований ентероколітичний синдром, білок-індукована ентеропатія, білок-індукований алергічний проктоколіт) і змішані, IgE- та не-IgE-опосередковані реакції (еозинофільний езофагіт, еозинофільний гастрит, еозинофільний гастроентерит). Гастроінтестинальні прояви харчової алергії також поєднуються із симптомами атопічних захворювань, частіше з атопічним дерматитом, кропив’янкою й ангіонабряком. Клінічні прояви алергічного ураження шлунково-кишкового тракту різноманітні та не є специфічними. До загальних ознак гастроінтестинальної алергії належать: блювання (виникає від декількох хвилин до 4–6 годин після прийому їжі); коліки (одразу чи через декілька годин після вживання їжі); запори; діарея; відмова від їжі (від конкретного продукту або взагалі від прийому їжі); абдомінальний біль; метеоризм, наявність слизу та еозинофілів у випорожненнях; зниження апетиту; головний біль. Зважаючи на неспецифічність клінічних проявів гастроінтестинальної харчової алергії, диференціальну діагностику слід проводити з такими захворюваннями, як захворювання й аномалії розвитку травної системи, психічні та метаболічні порушення, інтоксикації, інфекційні хвороби, недостатність ендокринної функції підшлункової залози, целіакія, муковісцидоз, імунодефіцити, дисахаридазна недостатність, побічна дія лікарських засобів, ендокринна патологія, синдром подразненого кишечника. Існуючі методи діагностики гастроінтестинальної алергії є обмеженими та недосконалими, що вимагає подальших наукових пошуків і досліджень, спрямованих на вчасне виявлення цієї патології, профілактику виникнення у генетично схильних дітей, розробку оптимальних алгоритмів діагностики, запобігання прогресуванню клінічних проявів, вибору індивідуальної дієтотерапії й адекватного медикаментозного лікування. В огляді літератури наведені сучасні погляди щодо діагностики гастроінтестинальної харчової алергії у дітей. Розглянуто клінічні прояви та діагностичні підходи до окремих видів гастроінтестинальної алергії залежно від механізму їх виникнення.

The Influence of Air Pollution on the Development of Allergic Inflammation in the Airways in Krakow’s Atopic and Non-Atopic Residents

Until now, the simultaneous influence of air pollution assessed by measuring the objective marker of exposition (1-hydroxypirene, 1-OHP) and atopy on the development of allergic airway diseases has not been studied. The aim of this study was to determine the pathomechanism of the allergic response to PM2.5 in atopic and non-atopic patients. We investigated the changes in peripheral blood basophil activity of patients after stimulation with the birch pollen allergen alone, the allergen combined with PM2.5 (BP), PM2.5 alone, a concentration of 1-OHP in urine, and a distance of residence from the main road in 30 persons. Activation by dust alone was positive for all concentrations in 83% of atopic and 75% of non-atopic assays. In the group of people with atopy, the simultaneous activation of BP gave a higher percentage of active basophils compared to the sum of activation with dust and birch pollen alone (B + P) for all concentrations. The difference between BP and B + P was 117.5 (p = 0.02) at a PM concentration of 100 μg. Such a relationship was not observed in the control group. The correlation coefficient between the distance of residence from major roads and urinary 1-OHP was 0.62. A Pearson correlation analysis of quantitative variables was performed, and positive correlation results were obtained in the atopy group between BP and 1-OH-P. Exposure to birch pollen and PM2.5 has a synergistic effect in sensitized individuals. The higher the exposure to pollutants, the higher the synergistic basophil response to the allergen and PM in atopic patients.

L-type amino acid transporter 1 is essential for Th2 cell-mediated allergic inflammation

Abstract L-type amino acid transporter 1 (LAT1), a transporter of large neutral amino acids, is rarely expressed in resting T cells, whereas its expression is remarkably upregulated upon activation. We have proven the essential role of T cells in the development of allergic inflammation in various target organs, though the contribution of LAT1 to T cell function in allergic diseases has not been clarified. Here, we investigated the effect of a LAT1 inhibitor, JPH203, on antigen-induced inflammatory responses in the skin, lungs, and nasal mucosa of immunized mice or mice transferred with in vitro-differentiated antigen-specific Th2 cells. Consistent with the augmented expression of LAT1 in skin-accumulated CD4+ T cells of atopic dermatitis patients, antigen-induced skin inflammation with eosinophil infiltration and Th2 cytokine production developed in immunized and Th2 cell-transferred mice was suppressed by JPH203 treatment. Essentially the same efficacy of JPH203 was seen in antigen-induced nasal eosinophilic inflammation accompanied by nasal hyperresponsiveness evoked in both mice. Remarkably, antigen-induced bronchial hyperresponsiveness was suppressed, whereas lung accumulation of eosinophils or antigen-specific T cells was not affected, by JPH203 in Th2 cell-transferred mice. The blockade of LAT1-mediated glycolysis, oxidative phosphorylation, and activating transcription factor 4-regulated amino acid starving responses in cytokine production and proliferation of Th2 was suggested to be involved in the efficacy of JPH203. LAT1 is essential for the pathogenesis of activated Th2 cell-mediated allergic inflammation and would be a promising target for the development of new means to treat allergic diseases.

Bidirectional sensory neuron-immune interactions: a new vision in the understanding of allergic inflammation.

Peripheral neurons (including sensory neurons) are ubiquitously distributed in all tissues, particularly at the interface with the environment. The primary function of sensory neurons is the transmission of sensations of temperature, pain and itch to elicit appropriate behavioral responses. More recently, sensory neurons have emerged as potent regulators of type 2 immune responses and allergic inflammation. There is increasing evidence showing that neurons can express receptors previously thought to be restricted to the immune compartment. In addition, certain subtypes of immune cells (e.g. mast cells, ILC2s or macrophages) also express specific neuroreceptors that provide them with the capacity to integrate neuron-derived signals and modulate their activation status during the development of allergic inflammation.

Suppressive effect of dexamethasone on murine Th9 cell-mediated nasal eosinophilic inflammation.

BackgroundTh9 cells have been implicated in the development of allergic inflammation, though its contribution to allergic rhinitis and the effect of steroid on Th9 cell-mediated nasal responses are unclear.ObjectiveIn this study, allergen-induced nasal inflammatory responses and their steroid responsiveness were investigated in ovalbumin (OVA)-specific Th9 cell-transferred mice.MethodsBALB/c mice were transferred with in vitro-differentiated Th9 cells and challenged by intranasal injection of OVA with or without subcutaneous administration of dexamethasone (Dex). Then, the infiltration of inflammatory cells in the nasal mucosa and nasal hyperresponsiveness (NHR) was assessed.ResultsThe significant NHR accompanied by nasal infiltration of eosinophils as well as allergen-specific T cells was induced in Th9 cell-transferred mice upon allergen challenge. These responses were strongly suppressed by the treatment with Dex.ConclusionThe participation of Th9 cells in the pathogenesis of allergic rhinitis was suggested.

Endogenous Maternal Lipids and Supplementation with Vitamin E Isoform Regulate Neonatal Dendritic Cells during Development of Allergic Disease

Background and Hypothesis: CDllb+CDllc+ dendritic cells (DCs) play a role in the development of allergic disease. It has been shown that of the vitamin E isoforms, α-Tocopherol decreases and γ-Tocopherol increases the generation of bone marrow-derived CD11b+CD11c+ DCs in vivo. And, in vivo experiments have also shown that β-glucosylceramides, endogenous maternal lipids, increase the neonate proliferation of this same subset of DCs. The mechanism for β-glucosylceramide regulation of these specific DC subsets is not known. Furthermore, it is also not known how vitamin E isoforms regulate DC development and differentiation. We determined whether α-tocopherol decreases and γ-tocopherol increases responses to β-glucosylceramide by regulating Protein Kinase C (PKC) activation during CDllb+CDllc+ DC differentiation and proliferation. 
 Project Methods: Cultured bone marrow cells (harvested from mice) were treated with lipid metabolites with and without supplementation of tocopherol isoforms, immunolabeled with antibodies that define DCs and with antibodies that detect active auto phosphorylated forms of PKC. Then, these cells were analyzed using flow cytometry. 
 Results: In vitro β-glucosylceramide elevated DC PKCα/β activity during CDllb+CDllc+ DC differentiation and proliferation/activation. Furthermore, these effects of β-glucosylceramide on DC PKCα/β activity were blocked by α-Tocopherol and elevated by γ-Tocopherol. 
 Potential Impact: These data provides a better understanding of how maternal β-glucosylceramide and dietary supplementation with vitamin E isoforms regulate DC proliferation and differentiation and ultimately development of allergic inflammation in offspring of allergic mothers.

Aplinkos veiksnių įtaka astmai bei kitoms alerginėms ligoms pasireikšti

Alerginės ligos – tai vienos labiausiai plintančių vaikų ligų Vakarų šalyse. Visiems gerai žinomi alergiją skatinamieji rizikos veiksniai (įvairūs alergenai, ksenobiotikai) bei veiksniai (mikrobai, dieta), kurie apsaugo nuo alergijos. Aplinkos tarša ir rūkymas tai pat turi įtakos minėtų veiksnių poveikiams ir kartu jie lemia genų ekspresijos pokyčiusmūsų organizme. Aplinkos ir genų sąveiką nagrinėja epigenetikosmokslas. Remiantis naujausiais genomo bei epigenomo tyrimais, straipsnyje apžvelgiami svarbiausi duomenys apie epigenetinių modifikacijų įtaką alerginiam uždegimui ir astmos pasireiškimui. Siekiama įrodyti, kokią didžiulę įtaką epigenetiniai pokyčiai gali turėti klinikiniams alergijos pasireiškimams ir kokia tai galėtų būti gera ateities diagnostikos priemonė. Pateikiami įrodymai dėl netolimos ateities epigenetikos analizės galimybių, vertinant imunoterapijos sėkmę bei astmos gydymo veiksmingumą. Naujos technologijos taip pat atveria galimybes inovatyviems gydymo metodams, pvz., epigenetiniam redagavimui.

Food and inhaled allergen sensitization range in children with atopyrelated gastrointestinal manifestations

The gastrointestinal tract is a barrier to the penetration of allergens into the organism and can be one of the shock organs of the development of allergic inflammation. The diagnosis of gastrointestinal manifestations of allergies is not given due attention, since their clinical symptoms are not pathognomonic, but are identical to diseases of the gastrointestinal tract of various genesis. The aim: to study the features of the structural and functional state of the gastrointestinal tract and the spectrum of sensitization to food and inhalation allergens of children with gastrointestinal manifestations of atopy. The analysis of medical histories of children with gastrointestinal manifestations of allergies aged from 1 to 18 years (n = 28), who were treated at the Regional children's allergological center in Krasnoyarsk, was performed. All patients underwent a specific allergological examination (allergological history, determination of the concentration of total IgE, specific IgE to food and inhalation allergens). The assessment of the state of the gastrointestinal tract was carried out taking into account complaints, anamnesis, objective examination and the results of esophagogastroduodenoscopy. It is established that gastrointestinal manifestations of atopy were most often combined with dermatorespiratory manifestations of allergy in the form of allergic rhinitis, atopic bronchial asthma and atopic dermatitis. Among the lesions of the gastrointestinal tract with the highest frequency of occurrence, changes in the nature of the stool (diarrhea, constipation) and the presence of symptoms of inflammation of the gastrointestinal tract-gastroesophageal reflux, gastritis, bulbitis, duodenitis, were determined. According to the results of esophagogastroduodenoscopy, gastritis and cardia insufficiency were most often determined. According to the results of the analysis of the concentration of total IgE in the blood serum, the increased level was determined in 42,8% of cases, the average value of total IgE in the blood serum in patients with atopic genesis of allergies was 140,9 IU/ml. These data evidence that the immunopathological basis for triggering allergic inflammation of the gastrointestinal tract may be based not only on atopic mechanisms. Based on the analysis of specific IgE concentrations, the characteristics of the spectrum of sensitization to food and inhalant allergens of children with gastrointestinal manifestations of atopy were determined. The most significant allergens were: food – flour mix; pollen – mixed of trees; domestic – perennial mixed. Thus, when conducting a specific allergological examination of children with atopy, it is necessary to take into account the systemic nature of the process and pay special attention to assessing the state of the gastrointestinal tract, as one of the shock organs in the development of allergic inflammation.

Luteolin reduces fluid hypersecretion by inhibiting TMEM16A in interleukin-4 treated Calu-3 airway epithelial cells.

Rhinorrhea in allergic rhinitis (AR) is characterized by the secretion of electrolytes in the nasal discharge. The secretion of Cl– and HCO3– is mainly regulated by cystic fibrosis transmembrane conductance regulator (CFTR) or via the calcium-activated Cl– channel anoctamin-1 (ANO1) in nasal gland serous cells. Interleukin-4 (IL-4), which is crucial in the development of allergic inflammation, increases the expression and activity of ANO1 by stimulating histamine receptors. In this study, we investigated ANO1 as a potential therapeutic target for rhinorrhea in AR using an ANO1 inhibitor derived from a natural herb. Ethanolic extracts (30%) of Spirodela polyrhiza (SPEtOH) and its five major flavonoids constituents were prepared. To elucidate whether the activity of human ANO1 (hANO1) was modulated by SPEtOH and its chemical constituents, a patch clamp experiment was performed in hANO1-HEK293T cells. Luteolin, one of the major chemical constituents in SPEtOH, significantly inhibited hANO1 activity in hANO1-HEK293T cells. Further, SPEtOH and luteolin specifically inhibited the calcium-activated chloride current, but not CFTR current in human airway epithelial Calu-3 cells. Calu-3 cells were cultured to confluency on transwell inserts in the presence of IL-4 to measure the electrolyte transport by Ussing chamber. Luteolin also significantly inhibited the ATP-induced increase in electrolyte transport, which was increased in IL-4 sensitized Calu-3 cells. Our findings indicate that SPEtOH and luteolin may be suitable candidates for the prevention and treatment of allergic rhinitis. SPEtOH- and luteolin-mediated ANO1 regulation provides a basis for the development of novel approaches for the treatment of allergic rhinitis-induced rhinorrhea.

Molecular and genetic mechanisms of endothelial dysfunction in children with allergic enteropathy

Objective. The objective is to analyze molecular and genetic mechanisms of endothelial dysfunction development in children with allergic enteropathy.Methods: We have studied the polymorphisms of endothelial nitric oxide synthase gene and the level of nitric oxide metabolites in coprofiltrates in 43 children aged from 6 months to 3 years with allergic enteropathy.Results: The endothelial dysfunction in allergic enteropathy is associated with nitric oxide molecule. Carriage of the homozygous allele СС Т786С of the endothelial nitric oxide synthase gene raises the risk of IgE-independent food allergy development by 8.8 times.Conclusions: The conducted study evidences the active participation of nitric-oxidergic mechanism in allergic inflammation development.

Activation of blood cells by LPS and DpE: the role of sMD-2 and p38 MAPK in the development of allergic inflammation

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Toll-like receptor-ligand induced thymic stromal lymphopoietin expression in primary equine keratinocytes.

Thymic stromal lymphopoietin (TSLP) plays a key role in the development of allergic inflammation. Little is known about possible triggers of equine TSLP expression. To investigate TSLP expression in equine insect bite hypersensitivity (IBH) skin lesions. The capacity of TLR 1-8 ligands (L) and of atopic cytokine milieu as potential triggers of TSLP and of interleukin (IL)-6 as a downstream effector molecule of TLR signalling, were examined in primary equine keratinocyte cultures. Lesional skin from IBH-affected and healthy skin from control-horses (n=9 each group) was sampled. Keratinocyte cultures were established from six healthy horses and stimulated with TLR 1-8-L, and with IL-4 and tumor necrosis factor-α, to mimic an atopic inflammation cytokine milieu. TSLP and IL-6 gene expression was assessed by quantitative real-time PCR. Expression of TSLP was significantly greater in IBH lesions compared to healthy skin. TLR 1-8-L significantly upregulated TSLP expression in keratinocytes. The strongest upregulation was induced by TLR 1/2-L and TLR 3-L. Combination of atopic cytokine milieu and TLR 1/2-L or TLR 3-L further increased TSLP expression. TLR-L 1-5 stimulation significantly upregulated IL-6 expression. The data herein suggest that the upregulation of TSLP expression in lesional skin of IBH-affected horses might play a role in IBH development. Moreover, TSLP expression is induced by TLR-L, in particular by TLR 1/2-L and TLR 3-L, and is further increased by atopic cytokine milieu, indicating a mechanism for TSLP-mediated exacerbation of IBH.