A beneficial environment promotes immune resilience through epigenetic regulation [scRNA-seq]
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE307573 | GEO | 2026/01/19
REPOSITORIES: GEO
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Project description:Environmental factors are often detrimental; however, certain environments enhance immune resilience. Notably, children raised on traditional farms show reduced allergies and asthma prevalence. Here, we investigated how a beneficial environment, using farm dust (FD) extract, influenced lung immune function in OVA-induced allergic inflammation. FD-exposure reduced allergic lung inflammation and increased monocyte-derived macrophage (MDM) recruitment. scRNA-seq revealed that FD-exposed MDMs had altered gene expression, including dampened Ccl8 and MHCII expression, impairing eosinophil recruitment and antigen presentation. RNA-seq and ATAC-seq confirmed FD-induced epigenetic reprogramming ex-vivo, on bone marrow-derived macrophages. This modulation, seen in both human and murine cells, relied on HDAC activity sustained by PPARγ signaling. These findings suggest that beneficial environmental exposures can reprogram immune cells and may offer a novel strategy for asthma prevention.
2026-01-19 | GSE308681 | GEO
Project description:Background: Farm exposures in early life reduce the risks for childhood allergic diseases and asthma. There is less information about how farm exposures relate to respiratory illnesses and mucosal immune development. Objective: We hypothesized that children raised in farm environments have a lower incidence of viral illnesses over the first two years of life than non-farm children. We also analyzed between farm exposures or respiratory illnesses were related to patterns of nasal cell gene expression. Methods: The Wisconsin Infant Study Cohort (WISC) birth cohort enrolled farm and non-farm pregnant women from central Wisconsin. Parents reported prenatal farm and other environmental exposures. Illness frequency and severity were assessed using illness diaries and periodic surveys. Nasopharyngeal cell gene expression at age two years was compared to farm exposure and respiratory illness history. Results: There was a higher rate of respiratory illnesses in the non-farm vs. farm group (rate ratio 0.82 [0.69,0.97], p=0.020), but no significant differences in wheezing illnesses. There was a stepwise reduction in rates of respiratory illnesses in children exposed at least weekly to 0, 1, or ≥2 animals (p=0.006). In analyzing nasal cell gene expression, farm exposures and preceding respiratory illnesses were positively related to gene signatures for mononuclear cells and innate and antimicrobial responses. Conclusions: Children exposed to farms and farm animals had lower rates of respiratory illnesses over the first two years of life. Both farm exposures and preceding respiratory illnesses were associated with increased innate immune responses, suggesting that these exposures stimulate mucosal immune responses to reduce subsequent illness frequency.
2024-01-29 | GSE233761 | GEO
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: Microbial interventions against allergic asthma have robust epidemiologic underpinnings and the potential to recalibrate disease-inducing immune responses. Oral administration of OM-85, a standardized lysate of human airways bacteria, is widely used empirically to prevent respiratory infections, and a clinical trial is testing its ability to prevent asthma in at-risk children. On the other hand, we previously showed that intra-nasal administration of products from microbe-rich farm environments abrogate experimental allergic asthma. Objectives: To investigate whether direct administration of OM-85 to the airway compartment protects against experimental allergic asthma, and to identify protective cellular and molecular mechanisms activated through this natural route. Methods: BALB/cJ mice (7-8 weeks old) sensitized and challenged with Ovalbumin received OM-85 intra-nasally, and cardinal cellular and molecular asthma phenotypes were measured. Murine lung gene expression was profiled by RNA-sequencing. Results: Airway administration of OM-85 suppressed allergic asthma and altered the transcriptome profile in unfractionated lung tissue. Conclusion We provide the first demonstration that administration of a standardized bacterial lysate to the airway compartment protects from experimental allergic asthma by engaging multiple immune pathways.
2021-10-19 | GSE167867 | GEO
Project description:In the first decade of life, high-asthma risk urban children develop stable phenotypes of respiratory health versus disease that link early life environmental exposures to childhood allergic sensitization and asthma. Moreover, unique patterns of nasal gene expression demonstrate how specific molecular pathways underlie distinct respiratory phenotypes, including allergic and non-allergic asthma.
2021-04-01 | GSE145505 | GEO
Project description:The development of extra-intestinal diseases is often accompanied by disruptions in intestinal microbiota and their metabolites. Improvement of the intestinal microenvironment frequently results in amelioration of these diseases, highlighting the need to identify key regulatory intestinal factors. In our asthma study, we identified intelectin-1 (ITLN1), predominantly expressed in the intestine, as a critical factor in maintaining intestinal bacterial homeostasis to mitigate allergic asthma via gut-bone-lung axis. We observed that reduced serum ITLN1 levels in asthmatic patients were significantly associated with increased disease severity and airway inflammation. In house dust mite (HDM)-induced asthma mouse model, ITLN1 deficiency exacerbated allergic inflammation by disrupting gut microbial homeostasis, resulting in decreased production of the beneficial short-chain fatty acid butyrate due to reduced Erysipelotrichaceae, Muribaculaceae, and Bifidobacteriaceae levels. Butyrate reduction increased CCL8 secretion by lung macrophages, which facilitated the recruitment of CD4+ T cells from the bone marrow to the lungs through the CCL8-CCR3 axis and enhanced group 2 innate lymphoid cells immune response, thereby amplifying type 2 inflammation. Elevated CCL8 levels were detected in both asthmatic patients and ITLN1-deficient asthmatic mice. Notably, supplementation with either ITLN1 or butyrate, as well as neutralization of CCL8, effectively attenuated lung allergic inflammation and improved asthma outcomes. Our findings establish ITLN1 as a crucial mediator that links gut microbial metabolism to pulmonary immune regulation, providing insights into the gut-bone-lung axis as a regulatory mechanism in asthma pathogenesis. These results position ITLN1 as a promising therapeutic target for modulating the intestinal microenvironment and mitigating systemic inflammatory responses in asthma and related disorders.
2025-12-09 | GSE281643 | GEO
Project description:Allergic diseases affect millions of people worldwide. An increase in their prevalence has been associated with alterations in the gut microbiome, i.e., the microorganisms and their genes within the gastrointestinal tract. Maturation of the infant immune system and gut microbiota occur in parallel; thus, the conformation of the microbiome may determine if tolerant immune programming arises within the infant. Here we show, using deeply phenotyped participants in the CHILD birth cohort (n = 1115), that there are early-life influences and microbiome features which are uniformly associated with four distinct allergic diagnoses at 5 years: atopic dermatitis (AD, n = 367), asthma (As, n = 165), food allergy (FA, n = 136), and allergic rhinitis (AR, n = 187). In a subset with shotgun metagenomic and metabolomic profiling (n = 589), we discover that impaired 1-year microbiota maturation may be universal to pediatric allergies (AD p = 0.000014; As p = 0.0073; FA p = 0.00083; and AR p = 0.0021). Extending this, we find a core set of functional and metabolic imbalances characterized by compromised mucous integrity, elevated oxidative activity, decreased secondary fermentation, and elevated trace amines, to be a significant mediator between microbiota maturation at age 1 year and allergic diagnoses at age 5 years (β<sub>indirect</sub> = -2.28; p = 0.0020). Microbiota maturation thus provides a focal point to identify deviations from normative development to predict and prevent allergic disease.
2024-10-24 | MTBLS7919 | MetaboLights
Project description:Asthma pathogenesis and susceptibility involves a complex interplay between genetic and environmental factors. We report the results of expression microarray studies using tissue obtained from bronchial biopsies of healthy controls and of subjects with allergic asthma, both before and following inhaled corticotherapy.
2009-04-24 | GSE15823 | GEO
Project description:Allergic asthma is a complex trait. Several approaches have been used to identify biomarkers involved in this disease. This study aimed at demonstrating the relevance and validity of microarrays in the definition of allergic asthma expression pattern. The authors compared the transcript expressions of bronchial biopsy of 2 different microarray experiments done 2 years apart, both including nonallergic healthy and allergic asthmatic subjects (n = 4 in each experiment). U95Av2 and U133A GeneChips detected respectively 89 and 40 differentially expressed genes. Fifty-five percent of the U133A genes were previously identified with the U95Av2 arrays. The immune signaling molecules and the proteolytic enzymes were the most preserved categories between the 2 experiments, because 3/4 of the genes identified by the U133A were also significant in the U95Av2 study for both categories. These results demonstrate the relevance of microarray experiments using bronchial tissues in allergic asthma. The comparison of these GeneChip studies suggests that earlier microarray results are as relevant as actual ones to target new genes of interest, particularly in function categories linked to the studied disease. Moreover, it demonstrates that microarrays are a valuable technology to target novel allergic asthma pathways as well as biomarkers. 4 healthy controls without history of allergy and asthma and 4 allergic asthmatic subjects according to the American Thoracic Society (ATS) criteria were selected
2012-10-18 | E-GEOD-41649 | biostudies-arrayexpress
Project description:The implication of alveolar macrophages (AM) in asthma, a Th2 disease, has not been well characterized. Thus, the goal of this study is to better characterize AM phenotype of allergic asthmatic compared with normal subjects using genomic expression analyses. Microarray analyses were performed with AM isolated from bronchoalveolar lavage. Robust multiarray analysis (RMA) normalization and Smythâs moderated t test were used to select differentially expressed genes. Fifty differentially expressed genes were identified. Nineteen have been classified in categories linked to stress or immune responses and among them; nine are part of the heat shock protein (HSP) family. Difference of expression for three (HSPD1, PRNP, SERPINH1) of the five selected genes were validated using real-time reverse transcriptionâpolymerase chain reaction. Enzyme linked immunosorbent assay was used to measure the protein level of heat shock protein 60 (HSP60), the protein encoded by HSPD1, and showed difference in AM protein level between allergic asthmatic and control subjects. In summary, this study suggests that HSP gene family, particularly HSP60, is involved in AM functions in a context of allergic asthma. These results also support the involvement of AM immune functions in the development of an allergic asthmatic response. Ten alveolar macrophage samples from bronchoalveolar lavages have been studied. Five of them are from allergic asthmatic subjects and five from control subjects (without allergy and asthma).
2010-07-29 | E-GEOD-22528 | biostudies-arrayexpress