Epigenomic analysis of primary human T cells reveals novel enhancers associated with Th2 memory differentiation and asthma susceptibility (3 cell types)
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE53643 | GEO | 2014/07/05
SECONDARY ACCESSION(S): PRJNA232542
REPOSITORIES: GEO
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Project description:A characteristic feature of asthma is the aberrant accumulation, differentiation or function of memory CD4+ T cells that produce Th2 cytokines (Th2 cells). By mapping genome-wide histone modification profiles of T cell subsets isolated from peripheral blood of healthy and asthmatic individuals, we identified enhancers with known and potential roles in the normal differentiation of human Th1 and Th2 cells. In addition, we discovered disease-specific T cell enhancers that differ between healthy and asthmatic individuals. Examination of H3K4me2 histone modifications in 3 human cell types in 11 healthy and 12 asthmatic individuals .
2014-07-05 | E-GEOD-53643 | biostudies-arrayexpress
Project description:A characteristic feature of asthma is the aberrant accumulation, differentiation or function of memory CD4+ T cells that produce Th2 cytokines (Th2 cells). By comparing gene expression profiles of T cell subsets isolated from peripheral blood of healthy and asthmatic individuals, we identified genes with known and potential roles in the normal differentiation of human Th1 and Th2 cells. Examination of gene expression in 3 human cell types in healthy and asthmatic individuals.
2014-07-05 | E-GEOD-55320 | biostudies-arrayexpress
Project description:A characteristic feature of asthma is the aberrant accumulation, differentiation or function of memory CD4+ T cells that produce Th2 cytokines (Th2 cells). By comparing gene expression profiles of T cell subsets isolated from peripheral blood of healthy and asthmatic individuals, we identified genes with known and potential roles in the normal differentiation of human Th1 and Th2 cells.
2014-07-05 | GSE55320 | GEO
Project description:Allergic asthma and rhinitis are two common chronic allergic diseases that affect the lungs and nose, respectively. Both diseases share clinical and pathological features characteristic of excessive allergen-induced type 2 inflammation, orchestrated by memory CD4+ T cells that produce type 2 cytokines (TH2 cells). However, a large majority of subjects with allergic rhinitis do not develop asthma, suggesting divergence in disease mechanisms. Since TH2 cells play a pathogenic role in both these diseases and are also present in healthy non-allergic subjects, we performed global transcriptional profiling to determine whether there are qualitative differences in TH2 cells from subjects with allergic asthma, rhinitis and healthy controls. TH2 cells from asthmatic subjects expressed higher levels of several genes that promote their survival as well as alter their metabolic pathways to favor persistence at sites of allergic inflammation. In addition, genes that enhanced TH2 polarization and TH2 cytokine production were also upregulated in asthma. Several genes that oppose T cell activation were downregulated in asthma, suggesting enhanced activation potential of TH2 cells from asthmatic subjects. Many novel genes with poorly defined functions were also differentially expressed in asthma. Thus, our transcriptomic analysis of circulating TH2 cells has identified several molecules that are likely to confer pathogenic features to TH2 cells that are either unique or common to both asthma and rhinitis.
2016-06-01 | GSE75011 | GEO
Project description:Polyfunctional Th2 cells play a crucial role in triggering diverse pathogenic responses in allergic diseases by producing multiple cytokines. However, the precise mechanism underlying their polyfunctionality remains elusive. In this study, we elucidate the pivotal role of Nrf2 in polyfunctional Th2 cells during allergic asthma. We found that an increase in reactive oxygen species (ROS) in immune cells infiltrating the lungs is necessary for the development of eosinophilic asthma. Deletion of the ROS sensor Nrf2 specifically in T cells, but not in dendritic cells, significantly abolished eosinophilia and polyfunctional Th2 cells in the airway. Mechanistically, Nrf2 intrinsic to T cells is essential for inducing optimal oxidative phosphorylation and glycolysis capacity, thereby driving Th2 cell polyfunctionality, partially by inducing PPARγ, independently of IL-33. Treatment with an Nrf2 inhibitor leads to a substantial decrease in polyfunctional Th2 cells and subsequent eosinophilia in mice, and a reduction in the production of Th2 cytokines from peripheral blood mononuclear cells (PBMCs) in asthmatic patients. These findings highlight the critical role of Nrf2 as a spatial and temporal metabolic hub that is essential for polyfunctional Th2 cells, suggesting potential therapeutic implications for allergic diseases.
2023-08-25 | GSE241355 | GEO
Project description:Airway epithelial brushings were obtained for microarray analysis by research bronchoscopy in 62 subjects with mild-to-moderate asthma not on inhaled steroids and 43 healthy controls. Asthma subjects were stratified into 2 subgroups, Th2 high and Th2 low asthma, based on their expression of a three-gene signature of Type 2 inflammation: POSTN, SERPINB2, and CLCA1. Gene expression comparisons were made between: 1. asthmatics and healthy controls, and 2. Th2 high asthma and Th2 Low asthma/Healthy controls. The gene expression alterations most associated with asthma were then used in gene set enrichment analyses and gene signature development to compare this asthma dataset to COPD gene expression datasets.
2015-04-01 | E-GEOD-67472 | biostudies-arrayexpress
Project description:Background: Most asthmatic patients have high serum levels of IgE directed against common environmental allergens such as house dust mite, animal danders and moulds. However the presence of specific IgE against individual allergens alone does not account for asthma. Many individuals are atopic but not asthmatic. Precise knowledge of the serum IgE specificity repertoire in asthmatic and non-asthmatic patients would substantially help in understanding the pathogenesis of the disease and at the same time facilitate the treatment and the implementation of preventive measures. Methods: We developed a microarray immunoassay containing 103 common allergens to study the IgE reactivity profiles of 485 asthmatic and 342 non-asthmatic individuals from families whose members had a documented history of asthma and atopy. The results were analyzed using k-means clustering to investigate whether IgE reactivity profiles correlated with asthma, disease severity and age of onset as well as with other atopic conditions such as rhinitis, conjunctivitis and eczema. We trained an artificial neural network (ANN) using the serum reactivity data to identify individuals as asthmatic and non-asthmatic. Results: Individual sera showed clear differences in the number and the combinations of allergens recognized as well as in the level of specific IgE. While the presence of specific IgE against single allergens correlated poorly with the pathological conditions examined k-means clustering analysis unraveled that a particular profile was significantly associated with asthma (p <1E-8). An ANN-based algorithm, calibrated with the profile reactivity data correctly classified as asthmatic or non-asthmatic 78% of the individual examined. Conclusions: Our analysis demonstrates that asthma may be a higher-order phenomenon related to patterns of response and not attributable to single antibody reactions. This information sheds new light on the risk of developing the disease and can be readily utilized in combination with an ANN-based tool to distinguish asthmatic and non-asthmatic individuals on the basis of their serum reactivity profile.
2012-01-03 | GSE20020 | GEO
Project description:Background: Most asthmatic patients have high serum levels of IgE directed against common environmental allergens such as house dust mite, animal danders and moulds. However the presence of specific IgE against individual allergens alone does not account for asthma. Many individuals are atopic but not asthmatic. Precise knowledge of the serum IgE specificity repertoire in asthmatic and non-asthmatic patients would substantially help in understanding the pathogenesis of the disease and at the same time facilitate the treatment and the implementation of preventive measures. Methods: We developed a microarray immunoassay containing 103 common allergens to study the IgE reactivity profiles of 485 asthmatic and 342 non-asthmatic individuals from families whose members had a documented history of asthma and atopy. The results were analyzed using k-means clustering to investigate whether IgE reactivity profiles correlated with asthma, disease severity and age of onset as well as with other atopic conditions such as rhinitis, conjunctivitis and eczema. We trained an artificial neural network (ANN) using the serum reactivity data to identify individuals as asthmatic and non-asthmatic. Results: Individual sera showed clear differences in the number and the combinations of allergens recognized as well as in the level of specific IgE. While the presence of specific IgE against single allergens correlated poorly with the pathological conditions examined k-means clustering analysis unraveled that a particular profile was significantly associated with asthma (p <1E-8). An ANN-based algorithm, calibrated with the profile reactivity data correctly classified as asthmatic or non-asthmatic 78% of the individual examined. Conclusions: Our analysis demonstrates that asthma may be a higher-order phenomenon related to patterns of response and not attributable to single antibody reactions. This information sheds new light on the risk of developing the disease and can be readily utilized in combination with an ANN-based tool to distinguish asthmatic and non-asthmatic individuals on the basis of their serum reactivity profile. The study consisted of a total of 872 sera samples: 485 individuals were diagnosed with asthma, 342 were classified as non asthmatic, a remaining 45 were classified as unconfirmed asthma diagnosis. The serum IgE reactivity profiles were analyzed against 103 allergens representative of 11 distinct allergen classes. Quantification of bound IgE: The fluorescence signal was acquired using ProScanArray Express™ version 3.0 software. PMC reading values of individual spots were corrected against the internal negative control to identify signals above background. Duplicate measurements of individual allergens were utilized. The signal collected from the allergens was interpolated with an external calibration curve to obtain the IU/ml value (see supplementary file GSE20020_IU_ml values.txt), and translated into a Class Score by plotting the data in a standard reactivity scale (see Sample data tables). Class Score values: (CLASS 0 (less than 0.35 IU/ml); CLASS 1 (0.35-0.7 IU/ml); CLASS 2 (0.71-3.5 IU/ml); CLASS 3 (3.51-17.5 IU/ml); CLASS 4 (17.51-50 IU/ml); CLASS 5 (50.01-100 IU/ml).
2012-01-03 | E-GEOD-20020 | biostudies-arrayexpress
Project description:The airway epithelium forms the interface between the inhaled environment and the lung. The airway epithelium is dysfunctional in asthma and epigenetic mechanisms are considered a contributory factor. We hypothesised that the DNA methylation profiles of cultured primary airway epithelial cells (AECs) would differ between cells isolated from individuals with asthma (n=17) versus those without asthma (n=16). AECs were isolated from patients by two different isolation techniques; pronase digestion (9 non-asthmatic, 8 asthmatic) and bronchial brushings (7 non-asthmatic and 9 asthmatic). DNA methylation was assessed using an Illumina Infinium HumanMethylation450 BeadChip array. DNA methylation of AECs clustered by isolation technique and linear regression identified 111 CpG sites differentially methylated between isolation techniques in healthy individuals. As a consequence, the effect of asthmatic status on DNA methylation was assessed within AEC samples isolated using the same technique. In pronase isolated AECs, 15 DNA regions were differentially methylated between asthmatics and non-asthmatics. In bronchial brush isolated AECs, 849 differentially methylated DNA regions were identified with no overlap to pronase regions. In conclusion, regardless of cell isolation technique, differential DNA methylation was associated with asthmatic status in AECs, providing further evidence for aberrant DNA methylation as a signature of epithelial dysfunction in asthma.
2019-10-31 | GSE137716 | GEO
Project description:Polyfunctional T cell responses are detrimental in immune disorders; however, it is unclear how effector T cell subsets acquire polyfunctionality in tissues. Here, we demonstrate that the activation of Nrf2 is necessary for the differentiation polyfunctional Th2 cells in vivo. Reactive oxygen species (ROS) levels are significantly elevated in lung-infiltrating immune cells during allergic asthma, and inhibiting either ROS or Nrf2 significantly decreases eosinophilia and polyfunctional Th2 cells in the lung. In vivo studies using multiple cell-type specific Nrf2-deficient mice and mixed bone marrow chimeras revealed that cell-intrinsic Nrf2 drives IL-5 and IL-13 expression in Th2 cells independently of IL-33. Mechanistically, Nrf2 promotes optimal OXPHOS and glycolysis capacity by inducing PPARg expression and glucose uptake to drive polyfunctionality of Th2 cells. Blocking Nrf2 reduces IL-5 and IL-13 production from house dust mite allergen-specific Th2 cells obtained from asthma patients. These findings demonstrate that Nrf2 acts as a spatiotemporal metabolic hub driving the differentiation of polyfunctional Th2 cells, which may have therapeutic implications for controlling allergic lung inflammation.
2023-08-24 | GSE241138 | GEO