Lung miRNA profiles show a time-of-day response in house dust mite-induced allergic asthma in mice.
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ABSTRACT:
SUBMITTER: Sundar IK
PROVIDER: S-EPMC8383904 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The increase in atopic diseases has occurred in such a short period of time that it becomes difficult to be attributed only to genetic factors, which usually need more prolonged time periods to manifest. In this setting during the last decade, the science of epigenetics has increasingly developed offering new perspectives and opening a new challenging research area. In this study we aimed to study the epigenetic patterns in B CD19+ Lymphocytes from healthy and allergic patients using the improved version of HELP assay.
2011-12-01 | GSE26080 | GEO
Project description:The increase in atopic diseases has occurred in such a short period of time that it becomes difficult to be attributed only to genetic factors, which usually need more prolonged time periods to manifest. In this setting during the last decade, the science of epigenetics has increasingly developed offering new perspectives and opening a new challenging research area. In this study we aimed to study the epigenetic patterns in B CD19+ Lymphocytes from healthy and allergic patients using the improved version of HELP assay. Our study focused specifically on DNA methylation in B CD19+ Lymphocytes isolated from whole blood of dust allergic patients (ALLERGY, n=3), aspirin intolerants (ASPIRIN INTOLERANT, n=3) and healthy subjects (CONTROL, n=3). We utilized a two-stage design involving genome-wide discovery followed by quantitative, single-locus validation. Each microarray consists of a two-color comparison of a methylation-sensitive representation of the genome (HpaII) with an internal methylation-insensitive control/reference (MspI).
2011-12-01 | E-GEOD-26080 | biostudies-arrayexpress
Project description:The efficacy of allergen immunotherapy (AIT) has been reported with different allergens including house dust mites (HDM). HDM are the most prevalent allergens in patients with asthma and/or rhinitis in China. In addition to improving symptoms, reducing medication need, and improving quality of life, AIT can change the course of allergic disease and induce allergen-specific immune tolerance. To date, the use of AIT is becoming more acceptable in China, and there are many studies about the current clinical practice immunotherapy. In this paper we discuss the main aspects of AIT undertaken in China; including symptom and medication scores, pulmonary function and airway hyperresponsiveness, specific allergen sensitivity, safety evaluation, and mechanisms underlying AIT. This review will provide some important information on AIT treatment strategies to doctors, healthcare professionals and organizations involved in the AIT in China. According to the studies in China, successful AIT may induce antibody responses and cellular reactions in relation to the significant improvement in clinical symptoms, reducing the need for medications and maintenance of stable pulmonary functions.
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Project description:While the pathogenesis of asthma is mainly orchestrated by antigen-specific Th2 cells and their cytokines, recent findings indicate the involvement of other subsets of helper T cells including Th17 cells. Previous studies have shown that IL-22, one of Th17 cell-related cytokines, plays multiple roles in regulating allergic airway inflammation; however, the mechanism underlying the Il-22-mediated regulation remains unclear. Here, we show that allergic airway inflammation upon intratracheal administration of house dust mite extract (HDM), a representative allergen, were exacerbated in IL-22-deficient mice. To address the molecular mechanisms by which IL-22 inhibits the development of HDM-induced allergic airway inflammation, we next performed an unbiased comprehensive screening of genes induced by IL-22 administration in the lung by RNA-seq analysis.
2017-08-10 | GSE100858 | GEO
Project description:It is unclear if allergen immunotherapy (AIT) can reduce allergy effector cell activation. We evaluated the basophil response during Dermatophagoides pteronyssinus (Der p) subcutaneous immunotherapy (SCIT) and its relationship to allergen-specific immunoglobulin G4 (sIgG4) in allergic rhinitis and/or asthma patients. The study included 55 subjects, of which 35 cases received Der p SCIT and 20 controls received standard medications. Symptom and medication scores (SMSs), sIgG4 levels, specific immunoglobulin E (sIgE) levels, allergen-induced basophil activation tests (BATs) in whole blood, and BAT inhibition assays in serum were determined at weeks 0, 4, 12, 16, 52, and 104 of SCIT. Levels of Der p sIgG4 in SCIT patients significantly increased after 12 weeks of treatment compared to week 0. Serum obtained from SCIT patients significantly inhibited basophil activation after 12 weeks of treatment. Removal of immunoglobulin G4 (IgG4) antibodies at week 104 reduced the ability of serum to block basophil activation. An increase of Der p sIgG4 rather than reduction of Der p sIgE correlated with the reduction of basophil activation during SCIT. The sIgG4 antibodies may compete with sIgE binding to allergens to form an immunoglobulin E (IgE)-allergen complex. SCIT reduced the sensitivity of allergen-triggered basophil activation in Der p allergic rhinitis and/or asthma patients through induction of sIgG4.
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Project description:Previous studies have shown that IL-22, one of the Th17 cell-related cytokines, plays multiple roles in regulating allergic airway inflammation caused by antigen-specific Th2 cells; however, the underlying mechanism remains unclear. Here, we show that allergic airway inflammation and Th2 and Th17 cytokine production upon intratracheal administration of house dust mite (HDM) extract, a representative allergen, were exacerbated in IL-22-deficient mice. We also found that IL-22 induces Reg3γ production from lung epithelial cells through STAT3 activation and that neutralization of Reg3γ significantly exacerbates HDM-induced eosinophilic airway inflammation and Th2 cytokine induction. Moreover, exostatin-like 3 (EXTL3), a functional Reg3γ binding protein, is expressed in lung epithelial cells, and intratracheal administration of recombinant Reg3γ suppresses HDM-induced thymic stromal lymphopoietin and IL-33 expression and accumulation of type 2 innate lymphoid cells in the lung. Collectively, these results suggest that IL-22 induces Reg3γ production from lung epithelial cells and inhibits the development of HDM-induced allergic airway inflammation, possibly by inhibiting cytokine production from lung epithelial cells.
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Project description:BackgroundThe SQ house dust mite (HDM) SLIT-tablet (ALK, Denmark) addresses the underlying cause of HDM respiratory allergic disease, and a clinical effect has been demonstrated for both HDM allergic rhinitis and allergic asthma. Here, we present pooled safety data from an adult population with HDM respiratory allergy, with particular focus on the impact of asthma on the SQ HDM SLIT-tablet tolerability profile.MethodsSafety data from 2 randomised double-blind, placebo-controlled clinical trials were included: MT-04: 834 adults with HDM allergic asthma not well controlled by inhaled corticosteroids and with HDM allergic rhinitis, and MT-06: 992 adults with moderate-to-severe HDM allergic rhinitis despite the use of allergy pharmacotherapy and with or without asthma.ResultsThe proportion of subjects experiencing adverse events (AEs) was greater in the active treatment group (12 SQ-HDM; 73% of subjects) compared to placebo (53%). The most common treatment-related AEs were local allergic reactions. No AEs were reported as systemic allergic reactions. Regardless of asthma status, most AEs were mild or moderate (>97% of AEs) and the frequency of serious AEs was low. Subgroup analysis revealed no statistically significant difference in the risk of experiencing moderate or severe treatment-related AEs for subjects with asthma compared to subjects without asthma (p = 0.88). In addition, subjects with partly controlled or uncontrolled asthma were no more likely to experience moderate or severe treatment-related AEs than subjects with controlled asthma (p = 0.42).ConclusionThe SQ HDM SLIT-tablet is well tolerated, and the safety profile was comparable for subjects with HDM respiratory allergic disease irrespective of asthma status.
| S-EPMC5804837 | biostudies-literature
Project description:BACKGROUND:Atopic status of the mother and maternal exposure to environmental factors are associated with increased asthma risk. Moreover, animal models demonstrate that exposure to allergens in strongly sensitized mothers influences offspring asthma development, suggesting that in utero exposures can influence offspring asthma. However, it is unclear whether maternal exposure to common human allergens such as house dust mite (HDM), in the absence of additional adjuvants, influences offspring asthma development. OBJECTIVE:We sought to determine whether maternal HDM exposure influences asthma development in offspring. METHODS:Pregnant female mice were exposed to PBS or HDM during pregnancy. Using offspring of PBS- or HDM-exposed mothers, the magnitude of HDM or Aspergillus fumigatus (AF) extract-induced airway hyperresponsiveness (AHR), airway inflammation, immunoglobulin production, TH2-associated cytokine synthesis, and pulmonary dendritic cell activity was assessed. RESULTS:Compared with offspring of PBS-exposed mothers, offspring of HDM-exposed mothers demonstrate increased AHR, airway inflammation, TH2 cytokine production, and immunoglobulin levels and a modest decrease in the phagocytic capacity of pulmonary macrophage populations following HDM exposure. Increased sensitivity to AF-induced airway disease was not observed. Offspring of HDM-exposed B-cell-deficient mothers also demonstrated increased HDM-induced AHR, suggesting that transfer of maternal immunoglobulins is not required. CONCLUSIONS:Our data demonstrate that maternal exposure to HDM during pregnancy increases asthma sensitivity in offspring in an HDM-specific manner, suggesting that vertical transmission of maternal immune responses may be involved. These findings have important implications for regulation of asthma risk, and suggest that exposure to HDM in the developed world may have underappreciated influences on the overall prevalence of allergic asthma.
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Project description:PURPOSE:Phosphoinositide 3-kinase (PI3K)-?-dependent Akt activation is known to play critical roles in various immune responses of white blood cells in which PI3K-? isoform is mostly expressed in contrast to the classes IA PI3Ks p110? and p110?. However, the immunological role of PI3K-? isoform is still controversial in airway epithelium under house dust mite (HDM)-induced allergic response. This study aimed to evaluate the role of PI3K-? isoform in HDM-induced allergic responses, focusing on NLRP3 inflammasome activation in airway epithelium. METHODS:We used wild-type mice and PI3K-? knock-out (KO) mice for HDM-induced asthma animal model and also performed in vitro experiments using primary cultured murine tracheal epithelial cells and human airway epithelial cells. RESULTS:PI3K-? activated HDM-induced NLRP3 inflammasome and epithelial cell-derived cytokines in the lung including airway epithelial cells. PI3K-? KO mice or knock-down of PI3K-? using siRNA exhibited the significant reduction in allergic asthmatic features and the suppression of NLRP3 inflammasome assembly as well as epithelial cell-derived cytokines. Interestingly, significantly increased expression of PI3K-? isoform was observed in stimulated airway epithelial cells and the increases in epithelial cell-derived cytokines were markedly suppressed by blocking PI3K-?, while these cytokine levels were independent of NLRP3 inflammasome activation. CONCLUSIONS:The results of this study suggest that PI3K-?-isoform can promote HDM-induced allergic airway inflammation via NLRP3 inflammasome-dependent response as well as via NLRP3 inflammasome-independent epithelial cell activation.
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Project description:Mounting evidence indicates that interleukin 17 (IL-17) is critically involved in the pathogenesis of severe asthma. We have previously reported that upon IL-17 stimulation, Act1, an IL-17-receptor-complex adaptor, directly binds to its target mRNAs and utilizes other proteins, such as HuR, to upregulate mRNA stability and translation. HuR mRNA targets include multiple asthma-related genes. In this study, we have used house dust mite (HDM), a natural allergen, to test the role of HuR in the pathogenesis of allergic asthma. We found that HuR deletion in airway epithelium diminished HDM-induced lung inflammation, including neutrophil and eosinophil infiltration. While Th2 cytokines were not altered, the production of CXCL1, CXCL5 and CCL11 chemokines was significantly diminished. Airway smooth muscle (ASM) cells contribute to the pathogenesis of allergic asthma by orchestrating inflammatory and remodeling responses. We found that IL-17 treatment of ASM cells induced translocation of HuR from nucleus to cytoplasm, where it bound directly to Cxcl1 and Ccl11 mRNA. Deletion of HuR in ASM cells decreased their proliferation as well as CXCL1 and CCL11 production in response to IL-17. Taken together, our findings demonstrate the importance of HuR-mediated regulation of gene expression to the pathogenesis of allergic asthma, in both airway epithelial and ASM cells.
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