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MRNAseq of human sputum macrophages and alveolar-like monocyte-derived macrophages of healthy controls and NSAID-exacerbated respiratory disease (N-ERD) patients

ABSTRACT: NSAID-exacerbated respiratory disease (N-ERD) represents a particularly severe endotype of chronic rhinosinusitis with nasal polyps (CRSwNP), which affects around 10-16% of CRSwNP patients. N-ERD is characterized by severe and refractory nasal polyposis, bronchial asthma and intolerance to non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin. Today, the pathogenesis of N-ERD remains incompletely understood and curative treatments are lacking. Macrophages are important source and target cells of arachidonic acid metabolites during type 2 inflammation, that have been neglected in N-ERD pathogenesis despite their presence in the nasal mucosa of N-ERD patients. Using a global transcriptomic approach, we identified systemic and local changes in macrophages between N-ERD patients and healthy controls. We isolated macrophages from induced sputum (sMac) and compared them to 7-days in vitro-differentiated, alveolar-like monocyte-derived macrophages (aMDM). Cells were lysed in RLT buffer with 1% beta-mercaptoethanol and stored at -80°C until RNA isolation and RNAseq. Since sMac yield of healthy controls was low, we pooled RNA of three donors (= sample S1) but excluded the data from subsequent analyses. Thus Analysis 1 shows the intra-group comparison of N-ERD sMac vs. N-ERD aMDM. In a second analysis (Analysis 2), we compared N-ERD aMDM vs. healthy control aMDM for transcriptome differences present in monocyte (blood)-derived cells.

INSTRUMENT(S): Illumina HiSeq 4000

ORGANISM(S): Homo sapiens

SUBMITTER: Pascal Haimerl

PROVIDER: E-MTAB-7965 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Whole-genome methylation profiling of monocytes and alveolar-like monocyte-derived macrophages from healthy controls and NSAID-exacerbated respiratory disease (N-ERD) patients

Project description:NSAID-exacerbated respiratory disease (N-ERD) represents a particularly severe endotype of chronic rhinosinusitis with nasal polyps (CRSwNP), which affects around 10-16% of CRSwNP patients. N-ERD is characterized by severe and refractory nasal polyposis, bronchial asthma and intolerance to non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin. Today, the pathogenesis of AERD remains incompletely understood and curative treatments are lacking. Macrophages are important source and target cells of arachidonic acid metabolites during type 2 inflammation, that have been neglected in N-ERD pathogenesis despite their presence in the nasal mucosa of N-ERD patients. Using a genome-wide methylomics approach, we identified persistent differences in monocytes and alveolar-like monocyte-derived macrophages (aMDM) between N-ERD patients and healthy controls. These were correlated with differentially expressed genes (DEGs) results from our whole transcriptome (RNAseq) analysis, available at: E-MTAB-7965 We isolated monocytes from venous blood and compared them to 7-days in vitro-differentiated aMDM. Cells were lysed in RLT buffer with 1% beta-mercaptoethanol and stored at -80°C until genomic DNA isolation and genome-wide methylomics analysis. Three data analyses were performed. Analyses 1 and 2 compared differentially methylated positions (DMPs) and regions (DMRs) between N-ERD and healthy monocytes or aMDM, respectively. Analysis 3 compared the N-ERD vs. healthy-specific differences between both cell types.

2020-07-31 | E-MTAB-8065 | biostudies-arrayexpress

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Project description:Chronic rhinosinusitis with nasal polyps (CRSwNP) is a debilitating inflammatory disease of the sinonasal cavities. Concomitant CRSwNP and asthma, together with hypersensitivity reactions to cyclooxygenase-1 (COX-1) inhibitors, is a particular phenotype known as NSAID-exacerbated respiratory disease (N-ERD), which is associated with greater disease severity. In this study, we attempted to characterize clinical, laboratory, and transcriptomic differences between CRSwNP patients with N-ERD (N-ERD; N=13) and CRSwNP patients without N-ERD (non-N-ERD, N=13).

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Expression data from ECRSwNP, non-ECRSwNP and control (miRNA)

Project description:Primarily on the basis of the absence or presence of nasal polyps (NPs)Chronic Rhinosinusitis(CRS) is often classified as CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). CRSwNP remains a signifificant public health problem with a considerable socioeconomic burden. The previous research reported that the pathophysiology of CRSwNP is a complex multifactorial disease. There have been many studies on its etiology, but its pathogenesis remains unclear. Dysregulated expression of miRNAs has been shown in psoriasis, rheumatoid arthritis, pulmonary fibrosis, and allergic asthma. CircRNA is also involved in the inflammatory diseases, such as in rheumatoid arthritis, septic acute kidney injury, myocardial ischemia/reperfusion injury, epsis-induced liver damage and so on. Especially, the function of miRNA is research hotspots, including in CRSwNP. While, the study on circRNA in CRSwNP is still unknown. Additionally, according to the different percentage of eosinophil, CRSwNP was further divided into eosinophilic CRSwNP (ECRSwNP) and non-ECRSwNP. However, little is known about the functions of circRNAs and miRNAs in CRSwNP. The study is aimed to investigate the expression of circular RNA (circRNA) and microRNA (miRNAs) in CRSwNP and control group, to conform whether these molecules are related with the occurrence and development of CRSwNP. We aimed to compare the microarray expression profile of miRNAs and circRNAs in nasal polyps of CRSwNP and normal nasal mucosa from control subjects.

2021-03-23 | GSE169376 | GEO

Expression data from ECRSwNP, non-ECRSwNP and control (CircRNA)

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Transcriptome analysis identifies Doublesex and Mab-3 Related Transcription Factor (DMRT3) in nasal polyp epithelial cells of patients suffering from Nonsteroidal anti-inflammatory drugs- Exacerbated Respiratory Disease (N-ERD)

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