Differential gene expression analysis in eosinophilic and mixed granulomatous lung inflammation
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ABSTRACT:
PROVIDER: PRJNA698791 | ENA |
REPOSITORIES: ENA
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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:Asthma is a complex, chronic respiratory disease with marked clinical and pathophysiological heterogeneity. Distinct inflammatory phenotypes of eosinophilic, mixed, neutrophilic and paucigranulocytic asthma are identified in patients, but most in vivo mouse models, studying asthma mechanisms, mimic only eosinophilic phenotype in humans. The detailed unbiased in vivo studies on molecular responses among different kinds of inflammation in asthma models are lacking. Therefore, we developed mouse models representing three different inflammatory phenotypes of airway inflammation, namely eosinophilic, mixed, and neutrophilic asthma via different methods of house dust mite sensitisation. We used microarrays to determine the global gene expression in the lungs of mice with eosinophilic, mixed and neutrophilic inflammatory phenotypes to uncover underlying differences in clinical presentation and to find novel molecular targets and pathways, which might reflect different molecular mechanisms of the disease. By whole genome transcriptome profiling, we found that airway tight junction (TJ) molecules, mucins and inflammasome-related genes are differentially expressed in distinct phenotypes of allergic airway inflammation. Next, detailed analysis of several molecules from these families by quantitative RT-PCR, western blot and confocal microscopy revealed that (i) Zo-1 and Cldn18 were downregulated in all phenotypes, while Cldn4 upregulation was characteristic for neutrophilic airway inflammation; (ii) mucins Clca1 (Gob5) and Muc5ac were upregulated in eosinophilic and even more in neutrophilic asthma, and (iii) upregulation of inflammasome-related molecules such as Nlrp3, Nlrc4, Casp-1 and IL-1b was characteristic for neutrophilic asthma. Finally, we showed that inflammasome/Th-17/neutrophilic axis cytokines, namely IL-1b and IL-17 impaired epithelial barrier function and increased mucins expressions in primary human bronchial epithelial cells from normal and asthmatic donors. Our findings suggest that differential expression of TJs, mucins and inflammasome-related molecules in distinct asthma phenotypes could be mechanistically linked and might further reflect the differences observed in the clinic.
2018-10-03 | GSE108417 | GEO
Project description:Granuloma annulare (GA) is an idiopathic condition characterized by granulomatous inflammation in the skin. Prior studies have suggested that GA develops from various triggers, leading to a complex interplay involving innate and adaptive immunity, tissue remodeling, and fibrosis. Macrophages are the major immune cells comprising GA granulomas, however, the molecular drivers and inflammatory signaling cascade behind macrophage activation is poorly understood. Histologically, GA exhibits both palisaded and interstitial patterns on histology, however the molecular composition of GA at the spatial level remains unexplored. GA is a condition without FDA-approved therapies despite the significant impact of GA on quality of life. Spatial transcriptomics is a valuable tool for profiling localized, genome-wide gene expression changes across tissue with emerging applications in clinical medicine. To improve our understanding of the spatially localized gene expression patterns underlying GA, we profiled the spatial gene expression landscape from six patients with GA. Our findings revealed mixed Th1 and Th2 signals comprising the GA microenvironment and spatially distinct M1 and M2 macrophage polarization characteristics. IFN- and TNF signals emerged as important regulators of GA granulomatous inflammation and interleukin-32 emerged as a key driver of granulomatous inflammation. Overall, our spatial transcriptomics data indicate that GA exhibits mixed immune and macrophage polarization.
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Project description:This study sought to evaluate the diffferential gene expression of human Eosinophilic Esophagitis (EoE) patients compared to control patients. Abstract from associated publication: Eosinophilic Esophagitis (EoE) is a chronic allergic disease characterized by progressive inflammation of the esophageal mucosa. While the transcriptome of EoE has been reported, few studies have examined the genetics among both adult and pediatric EoE populations. Here, we use microarray analysis to interrogate gene expression using esophageal biopsies from EoE and Control subjects with a wide age distribution. Analysis of differential gene expression and prediction of impaired pathways was compared using conventional transcriptome analysis programs and an artificial intelligence-based ADVAITA program. Principal Components Analysis revealed samples cluster by disease status (EoE and Control) irrespective of clinical features like sex, age, and disease severity. Global transcriptomic analysis revealed differential expression of several genes previously reported in EoE (CCL26, CPA3, POSTN, CTSC, ANO1, CRISP3, SPINK7). In addition, we identified differential expression of several genes from the MUC and SPRR families, which has not been previously reported. Our findings suggest their involvement in impaired barrier integrity and loss of epidermal cell differentiation in EoE patients. These findings present two new gene families that are differentially expressed in EoE patients in both adult and pediatric populations, which presents an opportunity for a future therapeutic targets that would be useful in a large demographic of patients.
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2014-11-01 | GSE44969 | GEO
Project description:Serum from children with active and inactive treated eosinophilic esophagitis was analyzed for detection of microRNA Individual serum samples from children with eosinophilic esophagitis were analyzed for detection of microRNA. (n=5 for active EoE and n=5 for inactive EoE)
2014-09-01 | E-GEOD-55793 | biostudies-arrayexpress
Project description:The goal of this study was to investigate and correlate differential methylation and expression in cells from the target organ in non-infectious granulomatous lung diseases, specifically sarcoidosis and chronic beryllium disease (CBD). To that end, cells were collected from patients via bronchoalveolar lavage (BAL), and extracted nucleic acids were hybridized to genome-wide arrays. We conclude that there are many genes that are both differentially methylated and expressed in the BAL fluid of patients with granulomatous lung disease. We identified 2,726 differentially methylated CpGs mapping to 1,944 unique genes when comparing CBD patients to beryllium-sensitized (BeS) individuals without disease. 69% of these genes were also differentially expressed in CBD. Sarcoidosis patients exhibited directional consistency at many loci, but genome-wide significance was not achieved, likely due to heterogeneity in the patient population.
2018-12-05 | GSE110777 | GEO
Project description:The goal of this study was to investigate and correlate differential methylation and expression in cells from the target organ in non-infectious granulomatous lung diseases, specifically sarcoidosis and chronic beryllium disease (CBD). To that end, cells were collected from patients via bronchoalveolar lavage (BAL), and extracted nucleic acids were hybridized to genome-wide arrays. We conclude that there are many genes that are both differentially methylated and expressed in the BAL fluid of patients with granulomatous lung disease. We identified 2,726 differentially methylated CpGs mapping to 1,944 unique genes when comparing CBD patients to beryllium-sensitized (BeS) individuals without disease. 69% of these genes were also differentially expressed in CBD. Sarcoidosis patients exhibited directional consistency at many loci, but genome-wide significance was not achieved, likely due to heterogeneity in the patient population.
2018-12-05 | GSE110776 | GEO
Project description:Significant recent progress has been made with understanding eosinophilic gastrointestinal disorders (EGIDs) yet most studies have focused on eosinophilic esophagitis (EoE). Herein, we aimed to provide fundamental information about the molecular characteristics of eosinophilic gastritis (EG).
2014-11-11 | GSE54043 | GEO
Project description:The goal of this study was to investigate and correlate differential methylation and expression in cells from the target organ in non-infectious granulomatous lung diseases, specifically sarcoidosis and chronic beryllium disease (CBD). To that end, cells were collected from patients via bronchoalveolar lavage (BAL), and extracted nucleic acids were hybridized to genome-wide arrays. We conclude that there are many genes that are both differentially methylated and expressed in the BAL fluid of patients with granulomatous lung disease. We identified 2,726 differentially methylated CpGs mapping to 1,944 unique genes when comparing CBD patients to beryllium-sensitized (BeS) individuals without disease. 69% of these genes were also differentially expressed in CBD. Sarcoidosis patients exhibited directional consistency at many loci, but genome-wide significance was not achieved, likely due to heterogeneity in the patient population.
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