Novel genes differentiating Eosinophilic Esophagitis (EoE) from GERD identified by RNA Sequencing
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE41687 | GEO | 2018/12/31
REPOSITORIES: GEO
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Project description:Esophageal biopsy RNA was isolated from proximal esophageal biopsied RNA from patients with EoE-like inflammatory diseases (EoE-like esophagitis, lymphocytic esophagitis, non-specific esophagitis), patients with active EoE, patients with GERD, and unaffected healthy controls. EoE-like inflammatory disease patients were clinically active at the time when biopsies were taken. None of the patients (EoE-like inflammatory diseases, EoE, GERD and controls) were under anti-eosinophil treatment (including dietary restrictions). The quality of the RNA-seq data was assessed using fastqc v. 0.11.5 1) and RSeQC v. 2.6.4 2). The reads were mapped to the reference genome using HiSat2 v. 2.1.0 3). FeatureCounts v. 1.6.0 4) was used to count the number of reads overlapping with each gene as specified in the genome annotation (Homo_sapiens.GRCh38.94). The Bioconducture package DESeq2 5) was used to test for differential gene expression between the experimental groups. TopGo 6) was used to identify gene ontology terms containing unusually many differentially expressed genes. An interactive Shiny application was set up to facilitate the exploration and visualisation of the RNA-seq results. All analyses were run in R version 3.4.4 (2018-03-15)
2022-02-28 | GSE148381 | GEO
Project description:Eosinophilic esophagitis (EoE) is an allergic inflammatory disease of the esophagus that occurs in both children and adults. Previous studies of affected tissue in pediatric cohorts have identified prominent signatures of eosinophilia and type 2 inflammation. However, the details of the immune response in adults with EoE are still being elucidated. To determine whether EoE in adults shares inflammatory profiles with those observed in children, we performed RNA-sequencing of paired esophageal biopsies and blood samples from adults with EoE or gastroesophageal reflux disease (GERD). Unbiased analysis of differentially expressed genes in tissue revealed a strong interferon signature that was significantly enriched in EoE patients as compared to patients with GERD. Both type I and type II interferon responsive genes were upregulated in adult biopsies, but not in blood. A similar increase in expression of interferon gene sets was observed in pediatric EoE biopsies as compared to non-EoE samples, and in public pediatric and adult RNA-sequencing data. Finally, we found that peripheral CD4+ T cells from children with EoE produce IFNG upon activation with EoE-causal allergens. Together, this work identifies a conserved interferon signature in pediatric and adult EoE, highlighting a role for non-type 2 inflammatory networks in the disease process.
2020-08-22 | GSE156651 | GEO
Project description:Esophageal biopsy RNA was isolated from distal esophageal biopsy RNA from EoE patients with active disease and from unaffected controls. EoE biopsies showed active disease pathology at the time when they were taken, and all patients reported no glucocorticoid treatment at the time of biopsy. RNA sequencing acquiring 50 million mappable 125 base-pair reads from paired-end libraries was performed at the Genetic Variation and Gene Discovery Core Facility at Cincinnati Children's Hospital Medical Center. Data were aligned to the hg19 build of the human genome using the Ensembl annotations as a guide for TopHat.
2019-06-16 | GSE113341 | GEO
Project description:To uncover molecular drivers of Eosinophilic Esophagitis (EoE), a global proteome screen of the esophageal biopsies from individuals with and without EoE was performed.
2023-08-01 | PXD040030 | Pride
Project description:Eosinophlic esophagitis (EoE) is increasely recognized as an antigen-drived disorder. The goal of this study is to reveal the gene expression changes in EoE before and after a successful glucocorticoid steroid treatment. We used microarrays to identify distinct genes involving the pathophysiology of EoE. Esophageal mRNA from the epithelial layers of 5 paired paraffin-embedded biopsies before and after treatment with glucocorticosteroids were harvested and profiled using Affymetrix Human Gene 1.0 ST array to generate differentially regulated mRNA transcripts.
2012-03-23 | E-GEOD-36725 | biostudies-arrayexpress
Project description:Background: Exposure of the esophageal mucosa to food allergens can cause acute mucosal responses in patients with eosinophilic esophagitis (EoE), but the underlying local immune mechanisms driving these acute responses are not well understood. Objective: To gain insight into the early transcriptomic changes that occur during an acute mucosal response to food allergens in EoE. Methods: Bulk RNA-sequencing was performed on esophageal biopsies from adult EoE patients (n = 5) collected before and 20 minutes after intramucosal injection of various food extracts in the esophagus. Baseline biopsies from non-EoE controls (n = 5) were also included. Results: At baseline, the transcriptome of the EoE patients showed increased expression of genes related to an EoE signature. After local food injection, we identified 40 genes with a potential role in the early immune response to food allergens (most notably CEBPB, IL1B, TNFSF18, PHLDA2, and SLC15A3). These 40 genes were enriched in processes related to immune activation, such as the acute phase response, cellular responses to external stimuli, and cell population proliferation. TNFSF18 (also called GITRL), a member of the TNF superfamily that is best studied for its co-stimulatory effect on T cells, was the most dysregulated early EoE gene showing a 12-fold increase compared with baseline and an 18-fold increase compared with a negative visual response. Further experiments showed that the esophageal epithelium may be an important source of TNFSF18 in EoE, which was rapidly induced by stimulating differentiated esophageal epithelial cells with the key EoE cytokine interleukin-13. Conclusion: Our data provide unprecedented insight into the transcriptomic changes that mediate the acute mucosal immune response to food allergens in EoE, and suggests that TNFSF18 may be an important effector molecule in this response.
2023-11-15 | GSE246323 | GEO
Project description:Eosinophilic esophagitis (EoE) is an allergic disorder characterized by the recruitment of eosinophils to the esophagus, resulting in chronic inflammation. We sought to understand the cellular populations present in the esophageal biopsies of patients with EoE and to determine how these populations are altered between active disease and remission. To this end, we analyzed cells from the esophageal biopsies, duodenal biopsies, and peripheral blood of EoE patients in active disease or remission using single-cell RNA and TCR sequencing. We identified gene modules regulated by transcription factors from the NF-κB family that characterize activated eosinophils in patients with active disease. Pathogenic effector Th2 (peTh2) cells present in the esophageal biopsies of patients with active disease expressed unique gene signatures associated with the synthesis of eicosanoids that are predicted to directly promote activation of tissue-resident eosinophils. The tissue-resident peTh2 population also exhibited clonal expansion, suggesting antigen-specific activation. Peripheral CRTH2+CD161- and CRTH2+CD161+ memory CD4+ T cells were enriched for either a conventional Th2 phenotype or a peTh2 phenotype, respectively. These cells also exhibited significant clonal expansion and convergence of TCR sequences, indicating that these cells are expanded in response to a defined set of antigens. The esophagus-homing receptor GPR15 was upregulated by peripheral peTh2 clonotypes that were also detected in the esophagus. Lastly, peTh2 cells and GPR15+ cells were enriched among milk-reactive CD4+ T cells in patients with milk-triggered disease, suggesting that peTh2 cells in EoE are an expanded, food antigen-specific population with enhanced esophagus homing potential.
2021-08-13 | GSE175930 | GEO
Project description:We utilized RNA sequencing to expand and better define the molecular entities involved in the transcriptional programming within the eosphagus in eosinophilic esophagitis (EoE) Examination of differentially expressed genes from RNA sequencing data performed on esophageal biopsy specimen from 6 healthy controls and 10 patients with active EoE
2014-06-27 | E-GEOD-58640 | biostudies-arrayexpress
Project description:Introduction Disruption of the epithelial barrier can induce eosinophilic esophagitis (EoE), a TH2-mediated food- and aeroallergen associated chronic inflammatory disease 1, 2. The expression of IL-20 subfamily cytokines, IL-19, IL-20 and IL-24, is increased in TH2-mediated diseases, yet their function in EoE is unknown. Methods Combining RNA-sequencing (RNA-seq) and proteome analysis, we have examined the effects of the IL-20 subfamily on esophageal epithelial cells using patient-derived organoids and an experimental EoE mouse model. Results When stimulated with IL-20 subfamily cytokines patient-derived esophageal organoids showed decreased expression of Filaggrin (FLG) and Filaggrin 2 (FLG2) responsible for epithelial cornification. In agreement, EoE patients with active inflammation showed elevated IL-20 subfamily cytokines and decreased FLG and FLG2 expression. Topical corticosteroid treatment in EoE patients restored filaggrin expression, while reducing IL-20 subfamily cytokines. Abolishment of IL-20 subfamily signalling in Il20R2-/- animals attenuated experimental EoE in an OVA-induced mouse model. In the esophageal keratinocyte cell line, KYSE-180, we identified IL-20 subfamily-induced STAT3 and MAPK (ERK1/2) pathway activation. However, Stat3fl/flKrt5cre mice with an epithelium specific deletion of Stat3 developed exacerbated experimental EoE with a pronounced decrease of Flg2. In line, combined stimulation of patient-derived esophageal organoids with IL-20 subfamily cytokines and pharmacological inhibition of STAT3 resulted in aggravated decrease of FLG and FLG2. In addition, pharmacological STAT3 inhibition resulted in reduced transepithelial electrical resistance (TEER) and increased macromolecular flux in patient-derived air liquid interface (ALI) cultures. Whereas, inhibition of the MAPK (ERK1/2) pathway hampered IL-20 subfamily induced TEER reduction and paracellular flux increment. Finally, MAPK (ERK1/2) inhibitor treatment reduced infiltrating CD45+ immune cells in the esophagus and alleviated experimental EoE in mice. Conclusion We discovered a novel regulatory function of the IL-20 subfamily for epithelial barrier integrity. Aberrant IL-20 subfamily signaling disturbs the epithelial barrier function, while abrogation of IL-20 subfamily and ERK1/2 signaling restores epithelial integrity and attenuates experimental EoE. Therefore, we propose that targeting the IL-20 subfamily pathway could present a novel therapeutic strategy for EoE treatment.
2023-05-10 | PXD031509 | Pride
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.
2023-08-10 | GSE228083 | GEO