Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA178960 | ENA |
REPOSITORIES: ENA
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Project description:Molecular profiling studies in asthma cohorts have identified a Th2-driven asthma subtype, characterized by elevated lower airway expression of POSTN, CLCA1 and SERPINB2. To assess upper airway gene expression as a potential biomarker for lower airway Th2 inflammation, we assayed upper airway (nasal) and lower airway (bronchial) epithelial gene expression, serum total IgE, blood eosinophils and serum periostin in a cohort of 54 allergic asthmatics and 30 matched healthy controls. 23 of 51 asthmatics in our cohort were classified as âTh2 highâ based on lower airway Th2 gene signature expression. Consistent with this classification, âTh2 highâ subjects displayed elevated total IgE and blood eosinophil levels relative to âTh2 lowâ subjects. Upper airway Th2 signature expression was significantly correlated with lower airway Th2 signature expression (r=0.44), with similar strength of association as serum total IgE and blood eosinophils, known biomarkers of Th2 inflammation. In an unbiased genome-wide scan, we identified 8 upper airway genes more strongly correlated with lower airway Th2 gene signature expression (r=0.58), including Eotaxin-3 (CCL26), Galectin-10 (CLC) and Cathepsin-C (CTSC). Asthmatics classified as âTh2 highâ using this 8-gene signature show similar serum total IgE and blood eosinophil levels as âTh2 highâ asthmatics classified using lower airway Th2 gene signature expression. We have identified an 8-gene upper airway signature correlated with lower airway Th2 inflammation, which may be used as a diagnostic biomarker for Th2-driven asthma. Upper airway (nasal) and lower airway (bronchial) epithelial brushings obtained from a cohort of 54 allergic asthmatics and 30 matched healthy controls were profiled by gene expression by microarray. Subjects were assayed for gene expression, serum total IgE, blood eosinophils and serum periostin.
2015-10-23 | E-GEOD-41861 | biostudies-arrayexpress
Project description:Molecular profiling studies in asthma cohorts have identified a Th2-driven asthma subtype, characterized by elevated lower airway expression of POSTN, CLCA1 and SERPINB2. To assess upper airway gene expression as a potential biomarker for lower airway Th2 inflammation, we assayed upper airway (nasal) and lower airway (bronchial) epithelial gene expression, serum total IgE, blood eosinophils and serum periostin in a cohort of 54 allergic asthmatics and 30 matched healthy controls. 23 of 51 asthmatics in our cohort were classified as ‘Th2 high’ based on lower airway Th2 gene signature expression. Consistent with this classification, ‘Th2 high’ subjects displayed elevated total IgE and blood eosinophil levels relative to ‘Th2 low’ subjects. Upper airway Th2 signature expression was significantly correlated with lower airway Th2 signature expression (r=0.44), with similar strength of association as serum total IgE and blood eosinophils, known biomarkers of Th2 inflammation. In an unbiased genome-wide scan, we identified 8 upper airway genes more strongly correlated with lower airway Th2 gene signature expression (r=0.58), including Eotaxin-3 (CCL26), Galectin-10 (CLC) and Cathepsin-C (CTSC). Asthmatics classified as ‘Th2 high’ using this 8-gene signature show similar serum total IgE and blood eosinophil levels as ‘Th2 high’ asthmatics classified using lower airway Th2 gene signature expression. We have identified an 8-gene upper airway signature correlated with lower airway Th2 inflammation, which may be used as a diagnostic biomarker for Th2-driven asthma.
2015-10-23 | GSE41861 | GEO
Project description:IL-5 is a key cytokine that plays an important role in the development of pathological conditions in chronic allergic inflammation. Identification of a strategy to inhibit IL-5 production is important for establishment of new therapies for allergic inflammation. We found that SH-2251, a novel thioamide-related compound, selectively inhibits the differentiation of IL-5-producing Th2 cells. SH-2251 inhibited the formation of the active histone modifications (H3K4me3, H3K9ac, H3K27ac) at the Il5 gene locus during Th2 cell differentiation. The recruitment of RNA polymerase II and the induction of Th2 cell-specific intergenic transcription between the Rad50 and Il5 gene locus was also inhibited. Furthermore, Th2 cell-driven airway inflammation in mice was suppressed by oral administration of SH-2251. We identified Gfi1 as a downstream target molecule of SH-2251 treatment. The expression of Gfi1 was dramatically decreased in SH-2251-treated Th2 cells. SH-2251-mediated inhibition of the IL-5-producing Th2 cell generation was restored by transduction of Gfi1. Thus, our study unearths SH-2251 as a novel therapeutic candidate for allergic inflammation that selectively inhibits IL-5 production. Gene expression in SH-2251-treated and untreated Th2 cells
2013-04-30 | E-GEOD-42131 | biostudies-arrayexpress
Project description:There is evidence for the beneficial effect of FK506, an effective immunosuppressive agent, for the treatment of asthma; however, the mechanisms underlying these effects are unclear. Using a mouse model of airway inflammation induced by Papain, a protease allergen, and RNAseq analysis of lung innate cells, we found that FK506 inhibited the activation of ILC2s, which initiate airway inflammation, as well as the induction of TH2 cells, which cause chronic inflammation. Our findings further support the clinical value of FK506 for the treatment of allergen-induced airway inflammation and clarify its targets and mechanisms of action.
2021-12-07 | GSE189918 | GEO
Project description:Rationale: Emerging evidence suggests that disease vulnerability is expressed throughout the airways; the so-called “unified airway hypothesis” but the evidence to support this is predominantly indirect. Objectives: To establish the transcriptomic profiles of the upper and lower airway and determine their level of similarity irrespective of airway symptoms (wheeze) and allergy. Methods: We performed RNA-sequencing on upper and lower airway epithelial cells from 63 children with or without wheeze and accompanying atopy, utilizing differential gene expression and gene co-expression analyses to determine transcriptional similarity. Results: We observed ~91% homology in the expressed between the two sites. When co-expressed genes were grouped into modules relating to biological functions, all were found to be conserved between the two regions, resulting in a consensus network containing 16 modules associated with ribosomal function, metabolism, gene expression, mitochondrial activity and anti-viral responses through interferon activity. Although symptom associated gene expression changes were more prominent in the lower airway, they were reflected in nasal epithelium and included; IL1RL1, PTGS1, CCL26 and POSTN. Through network analysis we identified a cluster of co-expressed genes associated with atopic-wheeze in the lower airway, which could equally distinguish atopic and non-atopic phenotypes in upper airway samples. Conclusions: We show that the upper and lower airway are significantly conserved in their transcriptional composition, and that variations associated with disease are present in both nasal and tracheal epithelium. Clinical Implication: Findings from this study supporting a unified airway imply that clinical insight regarding the lower airway in health and disease can be gained from studying the nasal epithelium.
2020-03-05 | GSE118761 | GEO
Project description:Alteration in the gene expression level in the lungs are thought to play a crucial role during the development of asthma and airway hyperresponsiveness. House dust mite induced allergic asthma is a Th2-lymphocyte driven inflammation characterized by airway hyperresponsiveness and eosinophilia while c-di-GMP, which is a potent mucosal adjuvant, induces a Th1-Th17 response accompanied by neutrophilia along with a low Th2 response. We aimed to identify changes in the expression of genes important in asthma pathology via targeted gene expression arrays.
2021-02-03 | GSE165969 | GEO
Project description:Defective interleukin-6 (IL-6) signaling has been associated with Th2 bias and elevated IgE. However, the underlying mechanism by which IL-6 may prevent the development of Th2-driven diseases remains unknown. Using a model of house-dust-mite (HDM)-induced Th2 differentiation and allergic airway inflammation, we show here that IL-6 signaling in allergen-specific T cells was required to prevent Th2 development and subsequent IgE response and allergic inflammation. Th2 cell lineage commitment required strong sustained IL-2 signaling. Importantly, we found that IL-6 turned off IL-2 signaling during early T cell activation and thus inhibited Th2 cell priming. Mechanistically, we found that IL-6-driven inhibition of IL-2 signaling in responding T cells was mediated by upregulation of suppressor of cytokine signaling 3 (SOCS3). Therapeutically, this mechanism can be mimicked by JAK1 inhibition. Collectively, our results identify an unrecognized mechanism that prevents the development of unwanted Th2 cell responses and associated diseases and outline potential preventive interventions.
2023-04-07 | GSE212158 | GEO
Project description:Although smoking-induced lung disease tends to be more common in the upper lobe, it is not known if this results from the skewed distribution of inhaled cigarette smoke or increased susceptibility of the upper lobes to these disorders. The distribution of inhaled cigarette smoke within the lung is complex, depending on lung pressure-volume relationships, gravity, individual smoking habits and the properties of the individual components of cigarette smoke. With the knowledge that the small airway epithelium is the earliest site of smoking-induced lung disease, and that the small airway epithelium is acutely sensitive to inhaled cigarette smoke with significant changes in the up- and down-regulation of hundreds of genes, we compared upper vs lower lobe gene expression in the small airway epithelium of the same cigarette smokers to determine if the gene expression patterns were similar or different. Active smokers (n=11) with early evidence of smoking-induced lung disease (normal spirometry but low diffusing capacity) underwent bronchoscopy and brushing of the small airway epithelium to compare upper vs lower lobe genome-wide gene expression assessed by microarray. Interestingly, cluster and principal component analysis demonstrated that, for each individual, the expression of the known small airway epithelium smoking-responsive genes were remarkably similar as upper vs lower lobe pairs, although, as expected, there were differences in the smoking-induced changes in gene expression from individual to individual. Thus, while there may be topographic differences in the distribution of cigarette smoke, sufficient smoke reaches the upper vs lower lobe small airway epithelium so that, within each smoker, the upper vs lower lobe gene expression are similar. These observations support the concept that the topographic differences in the occurrence of the smoking-induced lung diseases are likely secondary to topographic differences in the susceptibility of the upper vs lower lobes to cigarette smoke, not the topographic differences in distribution of inhaled cigarette smoke.
2017-03-08 | GSE26307 | GEO
Project description:The cystic fibrosis upper and lower airway metagenome
| PRJEB28553 | ENA
Project description:Comparison of the upper and lower airway microbiota
| PRJEB14074 | ENA