Microglia response to allergic airway inflammation during early postnatal period in mice
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PROVIDER: PRJNA669007 | ENA |
REPOSITORIES: ENA
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Project description:We examined how allergic inflammation in early postnatal period influences microglia using a short- and long-term airway allergy model. Male mice (C57BL/6) were immunized by intraperitoneal injection with aluminum hydroxide and ovalbumin (OVA) or phosphate-buffered saline (PBS) (control) at postnatal days (P) 3, 7, and 11, followed by intranasal challenge with OVA or PBS solution twice a week until P30 or P70. Microglia from whole brain were isolated from PBS- and OVA-treated mice by gating on CD11b+CD45int cells with flowcytometry at P30 and P70 respectively. Results suggest the dysregulation of microglial genes related to synaptic pruning and clearance, aging, and corticosteroid pathway and distinction between short- and long- term allergen challenge.
2023-10-11 | GSE159463 | GEO
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:Introduction: Prenatal and postnatal cigarette smoke exposure enhances the risk of developing asthma. Despite this as well as other smoking related risks, 11% of women still smoke during pregnancy. We hypothesized that cigarette smoke exposure during prenatal development generates long lasting differential methylation altering transcriptional activity that correlates with disease. Methods: In a house dust mite (HDM) model of allergic airway disease, we measured airway hyperresponsiveness (AHR) and airway inflammation between mice exposed prenatally to cigarette smoke (CS) or filtered air (FA). DNA methylation and gene expression were then measured in lung tissue. Results: We demonstrate that HDM-treated CS mice develop a more severe allergic airway disease compared to HDM-treated FA mice including increased AHR and airway inflammation. While DNA methylation changes between the two HDM-treated groups failed to reach genome-wide significance, 99 DMRs had an uncorrected p-value < 0.001. 6 of these 99 DMRs were selected for validation, based on the immune function of adjacent genes, and only 2 of the 6 DMRs confirmed the bisulfite sequencing data. Additionally, genes near these 6 DMRs (Lif, Il27ra, Tle4, Ptk7, Nfatc2, and Runx3) are differentially expressed between HDM-treated CS mice and HDM-treated FA mice. Conclusions: Our findings confirm that prenatal exposure to cigarette smoke is sufficient to modify allergic airway disease, however, it is unlikely that specific methylation changes account for the exposure-response relationship. These findings highlight the important role in utero cigarette smoke exposure plays in the development of allergic airway disease. Lung DNA methylation profiles of mice exposed in utero to cigarette smoke (CS) then treated with house dust mite (HDM, n = 8) or saline (n = 6), or exposed in utero to filtered air (FA) then treated with HDM (n = 9) or saline (n = 6)
2015-11-19 | E-GEOD-71718 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE35979: Gene expression data from IL13-induced allergic airway inflammation of mice lungs GSE35980: MicroRNA expression data from IL13-induced allergic airway inflammation of mice lungs GSE37079: Methylated DNA immunoprecipitation (MeDIP) microarray data from IL13-induced allergic airway inflammation of mouse lungs Refer to individual Series
2012-04-06 | E-GEOD-37085 | biostudies-arrayexpress
Project description:RATIONALE: The development and progression of asthma are strongly influenced by environmental exposures. We have demonstrated that mice exposed to a diet enriched with methyl donors during vulnerable periods of fetal development can enhance the heritable risk of allergic airway disease through epigenetic changes. OBJECTIVES: Since there is conflicting evidence on the role of folate in modifying allergic airway disease risk, we hypothesized that blocking folate metabolism through the loss of methylene-tetrahydrofolate reductase (MTHFR) activity would reduce the allergic airway disease phenotype. METHODS: Using a house dust mite (HDM) induced model of allergic airway disease, we tested the effect of MTHFR on disease severity. MEASUREMENTS AND MAIN RESULTS: Loss of MTHFR alters single carbon metabolite levels in the lung and serum including elevated homocysteine and cystathionine and reduced methionine. HDM-treated C57BL/6MTHFR-/- mice demonstrate significantly less airway hyerreactivity (AHR) compared to HDM-treated C57BL/6 mice. Furthermore, HDM-treated C57BL/6MTHFR-/- mice compared to HDM-treated C57BL/6 mice have reduced whole lung lavage (WLL) cellularity, eosinophilia, and IL-4/IL-5 cytokine concentrations. The effect of MTHFR loss on HDM-induced allergic airway disease was reversed by betaine supplementation. 737 genes are differentially expressed and 146 regions are differentially methylated in lung tissue from HDM-treated C57BL/6MTHFR-/- mice and HDM-treated C57BL/6 mice. Additionally, analysis of methylation/expression relationships identified 503 significant correlations. CONCLUSION: Collectively, these findings indicate that single carbon metabolism warrants further investigation as a disease modifier in allergic airway disease.
2018-01-31 | GSE71822 | GEO
Project description:Introduction: Prenatal and postnatal cigarette smoke exposure enhances the risk of developing asthma. Despite this as well as other smoking related risks, 11% of women still smoke during pregnancy. We hypothesized that cigarette smoke exposure during prenatal development generates long lasting differential methylation altering transcriptional activity that correlates with disease. Methods: In a house dust mite (HDM) model of allergic airway disease, we measured airway hyperresponsiveness (AHR) and airway inflammation between mice exposed prenatally to cigarette smoke (CS) or filtered air (FA). DNA methylation and gene expression were then measured in lung tissue. Results: We demonstrate that HDM-treated CS mice develop a more severe allergic airway disease compared to HDM-treated FA mice including increased AHR and airway inflammation. While DNA methylation changes between the two HDM-treated groups failed to reach genome-wide significance, 99 DMRs had an uncorrected p-value < 0.001. 6 of these 99 DMRs were selected for validation, based on the immune function of adjacent genes, and only 2 of the 6 DMRs confirmed the bisulfite sequencing data. Additionally, genes near these 6 DMRs (Lif, Il27ra, Tle4, Ptk7, Nfatc2, and Runx3) are differentially expressed between HDM-treated CS mice and HDM-treated FA mice. Conclusions: Our findings confirm that prenatal exposure to cigarette smoke is sufficient to modify allergic airway disease, however, it is unlikely that specific methylation changes account for the exposure-response relationship. These findings highlight the important role in utero cigarette smoke exposure plays in the development of allergic airway disease.
2015-11-19 | GSE71718 | GEO
Project description:RATIONALE: The development and progression of asthma are strongly influenced by environmental exposures. We have demonstrated that mice exposed to a diet enriched with methyl donors during vulnerable periods of fetal development can enhance the heritable risk of allergic airway disease through epigenetic changes. OBJECTIVES: Since there is conflicting evidence on the role of folate in modifying allergic airway disease risk, we hypothesized that blocking folate metabolism through the loss of methylene-tetrahydrofolate reductase (MTHFR) activity would reduce the allergic airway disease phenotype. METHODS: Using a house dust mite (HDM) induced model of allergic airway disease, we tested the effect of MTHFR on disease severity. MEASUREMENTS AND MAIN RESULTS: Loss of MTHFR alters single carbon metabolite levels in the lung and serum including elevated homocysteine and cystathionine and reduced methionine. HDM-treated C57BL/6MTHFR-/- mice demonstrate significantly less airway hyerreactivity (AHR) compared to HDM-treated C57BL/6 mice. Furthermore, HDM-treated C57BL/6MTHFR-/- mice compared to HDM-treated C57BL/6 mice have reduced whole lung lavage (WLL) cellularity, eosinophilia, and IL-4/IL-5 cytokine concentrations. The effect of MTHFR loss on HDM-induced allergic airway disease was reversed by betaine supplementation. 737 genes are differentially expressed and 146 regions are differentially methylated in lung tissue from HDM-treated C57BL/6MTHFR-/- mice and HDM-treated C57BL/6 mice. Additionally, analysis of methylation/expression relationships identified 503 significant correlations. CONCLUSION: Collectively, these findings indicate that single carbon metabolism warrants further investigation as a disease modifier in allergic airway disease.
2018-01-31 | GSE71821 | GEO
Project description:Fungal spores, abundant in the environment, are a major cause of asthma. But the precise host response that triggers fungal allergic airway inflammation remains unclear. We found that CD11c+ DCs and CD4+ T cells are essential for development of airway inflammation in mice when repeatedly exposed to inhaled spores. To delinate which DC subsets are mediating fungal allergic inflammation we undertook single cell RNAseq of DCs isolated from the lungs of mice exposed to fungal spores. This identified precise subsets altered upon spore exposure and following targeted removal identified distinct DC subsets (Mgl2+ cDC2s) that are essential for fungal allergic airway inflammation.
2024-12-04 | E-MTAB-13740 | biostudies-arrayexpress
Project description:Background: Inhalation exposure to biological particulate matter (BioPM) from livestock farms may provoke exacerbations in subjects suffering from allergy and asthma. The aim of this study was to use a murine model of allergic asthma to determine the effect of BioPM derived from goat farm on airway allergic responses Methods: Fine (< 2.5 μm) BioPM was collected from an indoor goat stable. Female BALB/c mice were ovalbumin (OVA) sensitized and challenged with OVA or saline as control. The OVA and saline groups were divided in sub-groups and exposed intranasally to different concentrations (0, 0.9, 3, or 9 μg) of goat farm BioPM. Bronchoalveolar lavage fluid (BALF), blood and lung tissues were collected. Results: In saline-challenged mice, goat farm BioPM alone induced a dose-dependent increase in neutrophils in BALF and induced production of macrophage inflammatory protein-3a). In OVA-challenged mice, BioPM significantly enhanced 1) inflammatory cells in BALF, 2) OVA-specific Immunoglobulin (Ig)G1, 3) interleukin-23 production, 4) airway mucus secretion-specific gene expression. RNAseq analysis of lungs indicates that neutrophil chemotaxis and oxidation-reduction processes were the representative genomic pathways in saline and OVA-challenged mice, respectively. Conclusions: A single exposure to goat farm BioPM enhanced airway inflammation in both saline and OVA-challenged allergic mice, with neutrophilic response as Th17 disorder and eosinophilic response as Th2 disorder indicative of the severity of allergic responses. Identification of the mode of action by which farm PM interacts with airway allergic pathways will be useful to design potential therapeutic approaches.
2020-08-01 | GSE148240 | GEO
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