Allergen induces pulmonary neuroendocrine hyperplasia in asthma
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE273687 | GEO | 2025/07/30
REPOSITORIES: GEO
Similar Datasets
Project description:Background: A specific subset of regulatory IL-10 producing B cells has been extensively studied in autoimmune and inflammatory pathologies. These cells are able to constrain exacerbated inflammation by inhibiting T cell mediated responses and maturation of antigen presenting cells. In allergic diseases, observations that increase of regulatory B cells is necessary for allergen tolerance suggest that development of allergic asthma would be associated with a defect in the regulatory B cells compartment. Objective: We sought to (i) characterize regulatory IL-10+ regulatory B cell subset in Balb/c mice by microarray and flow cytometry and (ii) investigate their regulatory capacity in vivo in a house dust mite model of allergic asthma. Results: We identified an IL-10 producing B cells subset able to control T cell proliferation in vitro in both control and asthmatic mice. This subset is decreased in allergic mice. IL-10+ Breg cells express high levels of CD9 and upregulate CD70 and CD73 after activation. Expression of CD9 allows identifying more than 50% of Bregs. Interestingly CD9+ B cells inhibit TH2-TH17 allergic airway inflammation in vivo after adoptive transfer in an IL-10 dependent manner. Conclusions: Herein, we demonstrate that induction of allergic asthma dampens the generation of Bregs contributing to exacerbated airway inflammation. We identified a distinct CD9+ Breg-cell population decreased in lung of HDM mice and able to control asthma and allergic airway inflammation by producing IL-10 after adoptive transfer. This study points B cells as an interesting therapeutic target in allergic asthma. IL-10+ B cells (n=3) and 3 IL-10- B cells (n=3) in control mice + IL-10+ B cells (n=3) and 3 IL-10- B cells (n=3) from asthmatic allergic (HDM) mice
2015-03-01 | E-GEOD-57772 | biostudies-arrayexpress
Project description:While the pathogenesis of asthma is mainly orchestrated by antigen-specific Th2 cells and their cytokines, recent findings indicate the involvement of other subsets of helper T cells including Th17 cells. Previous studies have shown that IL-22, one of Th17 cell-related cytokines, plays multiple roles in regulating allergic airway inflammation; however, the mechanism underlying the Il-22-mediated regulation remains unclear. Here, we show that allergic airway inflammation upon intratracheal administration of house dust mite extract (HDM), a representative allergen, were exacerbated in IL-22-deficient mice. To address the molecular mechanisms by which IL-22 inhibits the development of HDM-induced allergic airway inflammation, we next performed an unbiased comprehensive screening of genes induced by IL-22 administration in the lung by RNA-seq analysis.
2017-08-10 | GSE100858 | GEO
Project description:Levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, are increased in lung, sputum, exhaled breath condensate and plasma samples from asthma patients. ADMA is metabolized primarily by dimethylarginine dimethylaminohydrolase 1 (DDAH1) and DDAH2. We determined the effect of DDAH1 overexpression on development of allergic inflammation in mouse models of asthma. Wild type and DDAH1-transgenic mice were challenged with PBS or house dust mite (HDM). Airway inflammation was assessed by bronchoalveolar lavage (BAL) total and differential cell counts. Gene expression in lungs was determined by RNA-Seq and RT-quantitative PCR (qPCR). The expression of DDAH1 and DDAH2 was decreased in the lungs of mice following HDM exposure. Transgenic overexpression of DDAH1 resulted in decreased BAL total cell and eosinophil numbers following HDM exposure. Total IgE levels in serum and BAL fluid were decreased in HDM-exposed DDAH1-transgenic mice compared to HDM-exposed wild type mice. RNA-Seq results showed downregulation of genes in inducible nitric oxide synthase (iNOS) signaling pathway in PBS-treated DDAH1 transgenic mice versus PBS-treated wild type mice and downregulation of genes in IL-13/FOXA2 signaling pathway in HDM-treated DDAH1 transgenic mice versus HDM-treated wild type mice. Our findings suggest that decreased expression of DDAH1 in airway epithelial cells may contribute to allergic asthma and overexpression of DDAH1 attenuates allergen-induced airway inflammation through modulation of Th2 responses. mRNA profiles of WT and DDAH1-transgenic mice treated with PBS or house dust mite (HDM).
2013-12-03 | E-GEOD-49047 | biostudies-arrayexpress
Project description:Obesity is associated with severe, difficult to control asthma, and increased airway oxidative stress. Mitochondrial reactive oxygen species (mROS) are an important source of oxidative stress leading us to hypothesize that targeting mROS in obese allergic asthma might be an effective treatment strategy. Using a mouse model of house dust mite (HDM) induced allergic airway disease in mice fed a low- (LFD) or high-fat diet (HFD), and the mitochondrial antioxidant MitoQuinone (MitoQ); we investigated the effects of obesity and mROS on airway inflammation, remodelling and airway hyperreactivity (AHR). HDM induces airway inflammation, remodelling and hyperreactivity in both lean and obese mice. Obese allergic mice showed increased lung tissue eotaxin levels, airway tissue eosinophilia and AHR when compared to lean allergic mice. MitoQ reduced markers of airway inflammation, remodelling and hyperreactivity in both lean and obese allergic mice, and tissue eosinophilia in obeseHDM mice. mROS regulates cell signalling by protein oxidation of multiple downstream targets: MitoQ reduced HDM-induced cysteine-sulfenylation of several proteins including those involved in the unfolded protein response (UPR). In summary, mROS mediates the development of allergic airway disease and hence MitoQ might be effective for the treatment for asthma, and specific features of obese asthma.
2023-06-02 | PXD029715 | Pride
Project description:CD4+ helper T cells (TH) and regulatory T cells (Treg) that respond to common allergens play an important role in driving and dampening airway inflammation in patients with asthma. Until recently, direct, unbiased molecular analysis of allergen-reactive TH and Treg cells has not been possible. To better understand the diversity of these T cell subsets in allergy and asthma, we analyzed the single-cell transcriptome of ~50,000 house dust mite (HDM) allergen-reactive TH cells and Treg cells from asthmatics with HDM allergy and from three control groups: asthmatics without HDM allergy and non-asthmatics with and without HDM allergy. Our analyses show that HDM allergen-reactive TH and Treg cells are highly heterogeneous, and certain subsets are quantitatively and qualitatively different in subjects with HDM-reactive asthma. The number of interleukin (IL)-9 expressing HDM-reactive TH cells is greater in asthmatics compared with non-asthmatics with HDM allergy, and display enhanced pathogenic properties. More HDM-reactive Th and Treg cells expressing the interferon-response signature (THIFNR and TregIFNR) are present in asthmatics without HDM allergy compared with those with HDM allergy. In cells from these subsets (THIFNR and TregIFNR), expression of TNFSF10 was enriched; its product, TRAIL, dampens activation of TH cells. These findings suggest that the THIFNR and TregIFNR subsets may dampen allergic responses, which may help explain why only some people develop TH2 responses to nearly ubiquitous allergens.
2020-06-10 | GSE146170 | GEO
Project description:CD4+ helper T cells (TH) and regulatory T cells (Treg) that respond to common allergens play an important role in driving and dampening airway inflammation in patients with asthma. Until recently, direct, unbiased molecular analysis of allergen-reactive TH and Treg cells has not been possible. To better understand the diversity of these T cell subsets in allergy and asthma, we analyzed the single-cell transcriptome of ~50,000 house dust mite (HDM) allergen-reactive TH cells and Treg cells from asthmatics with HDM allergy and from three control groups: asthmatics without HDM allergy and non-asthmatics with and without HDM allergy. Our analyses show that HDM allergen-reactive TH and Treg cells are highly heterogeneous, and certain subsets are quantitatively and qualitatively different in subjects with HDM-reactive asthma. The number of interleukin (IL)-9 expressing HDM-reactive TH cells is greater in asthmatics compared with non-asthmatics with HDM allergy, and display enhanced pathogenic properties. More HDM-reactive Th and Treg cells expressing the interferon-response signature (THIFNR and TregIFNR) are present in asthmatics without HDM allergy compared with those with HDM allergy. In cells from these subsets (THIFNR and TregIFNR), expression of TNFSF10 was enriched; its product, TRAIL, dampens activation of TH cells. These findings suggest that the THIFNR and TregIFNR subsets may dampen allergic responses, which may help explain why only some people develop TH2 responses to nearly ubiquitous allergens.
2020-06-10 | GSE146046 | GEO
Project description:Previous studies have demonstrated that TET1 plays a protective role against house dust mite (HDM)-induced allergic airway inflammation. TET1 transcriptionally responded to HDM extract and regulated the expression of genes involved in asthma in human bronchial epithelial cells (HBECs). How TET1 regulates expression of these genes, however, is unknown. To this end, we measured mRNA expression, DNA methylation, chromatin accessibility and histone modifications in control and TET1 knockdown HBECs treated or untreated with HDM extract. Throughout our analyses of multi-omics data, we detected significant similarities between the effects of TET1 knockdown alone and the effects of HDM treatment alone, all enriched for asthma-related genes and pathways. One especially striking pattern was that both TET1 knockdown and HDM treatment generally led to decreased chromatin accessibility at many of the same genomic loci. Transcription factor enrichment analyses indicated that altered chromatin accessibility following the loss of TET1 may affect, or be affected by, CTCF and CEBP binding. Analysis of H3K27ac levels and comparison with existing datasets suggested a potential impact of TET1 on enhancer activity. TET1 loss also led to changes in DNA methylation, but these changes were generally in regions where accessibility was not changing. Lastly, more significant transcriptomic changes were observed in HBEC cells with TET1 knockdown compared to control cells following HDM challenges. Collectively, our data suggest that TET1 regulates gene expression through distinct mechanisms across various genomic regions in airway epithelial cells, restricting transcriptomic responses to allergen and potentially protecting against the development of asthma.
2025-05-30 | GSE293176 | GEO
Project description:Previous studies have demonstrated that TET1 plays a protective role against house dust mite (HDM)-induced allergic airway inflammation. TET1 transcriptionally responded to HDM extract and regulated the expression of genes involved in asthma in human bronchial epithelial cells (HBECs). How TET1 regulates expression of these genes, however, is unknown. To this end, we measured mRNA expression, DNA methylation, chromatin accessibility and histone modifications in control and TET1 knockdown HBECs treated or untreated with HDM extract. Throughout our analyses of multi-omics data, we detected significant similarities between the effects of TET1 knockdown alone and the effects of HDM treatment alone, all enriched for asthma-related genes and pathways. One especially striking pattern was that both TET1 knockdown and HDM treatment generally led to decreased chromatin accessibility at many of the same genomic loci. Transcription factor enrichment analyses indicated that altered chromatin accessibility following the loss of TET1 may affect, or be affected by, CTCF and CEBP binding. Analysis of H3K27ac levels and comparison with existing datasets suggested a potential impact of TET1 on enhancer activity. TET1 loss also led to changes in DNA methylation, but these changes were generally in regions where accessibility was not changing. Lastly, more significant transcriptomic changes were observed in HBEC cells with TET1 knockdown compared to control cells following HDM challenges. Collectively, our data suggest that TET1 regulates gene expression through distinct mechanisms across various genomic regions in airway epithelial cells, restricting transcriptomic responses to allergen and potentially protecting against the development of asthma.
2025-05-30 | GSE293175 | GEO
Project description:Previous studies have demonstrated that TET1 plays a protective role against house dust mite (HDM)-induced allergic airway inflammation. TET1 transcriptionally responded to HDM extract and regulated the expression of genes involved in asthma in human bronchial epithelial cells (HBECs). How TET1 regulates expression of these genes, however, is unknown. To this end, we measured mRNA expression, DNA methylation, chromatin accessibility and histone modifications in control and TET1 knockdown HBECs treated or untreated with HDM extract. Throughout our analyses of multi-omics data, we detected significant similarities between the effects of TET1 knockdown alone and the effects of HDM treatment alone, all enriched for asthma-related genes and pathways. One especially striking pattern was that both TET1 knockdown and HDM treatment generally led to decreased chromatin accessibility at many of the same genomic loci. Transcription factor enrichment analyses indicated that altered chromatin accessibility following the loss of TET1 may affect, or be affected by, CTCF and CEBP binding. Analysis of H3K27ac levels and comparison with existing datasets suggested a potential impact of TET1 on enhancer activity. TET1 loss also led to changes in DNA methylation, but these changes were generally in regions where accessibility was not changing. Lastly, more significant transcriptomic changes were observed in HBEC cells with TET1 knockdown compared to control cells following HDM challenges. Collectively, our data suggest that TET1 regulates gene expression through distinct mechanisms across various genomic regions in airway epithelial cells, restricting transcriptomic responses to allergen and potentially protecting against the development of asthma.
2025-05-30 | GSE293178 | GEO
Project description:In recent years, alveolar macrophages (AM) have been shown to play an important role in environmental allergen-induced airway inflammation in asthma. In this study, we investigated the effect of house dust mite (HDM) and lipopolysaccharide (LPS) challenge on the transcriptome of AM from patients with mild asthma. We have shown previously that intrabronchial HDM/LPS challenge induces a mixed eosinophilic and neutrophil airways inflammation in asthma patients(5). Therefore, we hypothesize that exposure of AM to HDM/LPS would upregulate genes associated with eosinophil and neutrophil signaling. AM were harvested from the bronchoalveolar fluid of 8 asthma patients who were challenged with either saline in one lung segment or HDM/LPS in the contralateral lung segment. We performed RNA sequencing and found over 1000 significantly different expressed genes following HDM/LPS challenge. To the best of our knowledge, this is the first investigation to examine gene expression profiles in AM from asthma patients challenged with HDM and LPS in vivo. Using a well-controlled study design allowing paired analysis of saline and HDM/LPS effects in the same patient, we identified different transcriptional profiles in AM as consequence of local exposure to HDM and LPS. These findings may provide a better understanding of AM functions in (exacerbations of) allergic asthma.
2021-03-16 | GSE144576 | GEO