MAP3K8 is a major regulator of inflammation in human airway epithelial cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA407890 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Rationale: Aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, has been considered as an important regulator for immune diseases. We have previously shown that AhR protects against allergic airway inflammation. The underlying mechanism, however, remains undetermined. Objectives: We sought to determine whether AhR specifically in Type II alveolar epithelial cells (AT2) modulates allergic airway inflammation and its underlying mechanisms. Methods: The role of AhR in AT2 cells in airway inflammation was investigated in a mouse model of asthma with AhR conditional knock out mice in AT2 cells (Sftpc-Cre;AhRflox/flox). The effect of AhR on allergen-induced autophagy was examined by both in vivo and in vitro analyses. The involvement of autophagy in airway inflammation was analyzed by using autophagy inhibitor chloroquine. The AhR-regulated gene profiling in AT2 cells was also investigated by RNA-seq analysis. Results: Sftpc-Cre; AhRflox/flox mice showed exacerbation of allergen-induced airway hyperresponsiveness and airway inflammation with elevated Th2 and airway epithelial-derived cytokines in bronchoalveolar lavage fluid (BALF). Notably, an increased allergen-induced autophagy was observed in the lung tissues of Sftpc-Cre; AhRflox/flox mice when compared with wild-type mice. Further analyses suggested a functional axis of AhR-TGF-β1 that is critical in driving allergic airway inflammation through regulating allergen-induced cellular autophagy. Furthermore, inhibition of autophagy suppressed allergic airway inflammation with decreased Th2 and epithelial cell-derived cytokines in BALFs. Additionally, RNA-seq analysis suggests that autophagy is one of the major pathways and CALCOCO2/NDP52 and S1009 are major autophagy-associated genes in AT2 cells that contribute to the AhR-mediated allergic airway inflammation. Conclusion: These results suggest that AhR in AT2 cells functions as a protective mechanism against allergic airway inflammation through controlling cell autophagy.
2022-06-13 | GSE205818 | GEO
Project description:Molecular profiling studies in asthma cohorts have identified a Th2-driven asthma subtype, characterized by elevated lower airway expression of POSTN, CLCA1 and SERPINB2. To assess upper airway gene expression as a potential biomarker for lower airway Th2 inflammation, we assayed upper airway (nasal) and lower airway (bronchial) epithelial gene expression, serum total IgE, blood eosinophils and serum periostin in a cohort of 54 allergic asthmatics and 30 matched healthy controls. 23 of 51 asthmatics in our cohort were classified as âTh2 highâ based on lower airway Th2 gene signature expression. Consistent with this classification, âTh2 highâ subjects displayed elevated total IgE and blood eosinophil levels relative to âTh2 lowâ subjects. Upper airway Th2 signature expression was significantly correlated with lower airway Th2 signature expression (r=0.44), with similar strength of association as serum total IgE and blood eosinophils, known biomarkers of Th2 inflammation. In an unbiased genome-wide scan, we identified 8 upper airway genes more strongly correlated with lower airway Th2 gene signature expression (r=0.58), including Eotaxin-3 (CCL26), Galectin-10 (CLC) and Cathepsin-C (CTSC). Asthmatics classified as âTh2 highâ using this 8-gene signature show similar serum total IgE and blood eosinophil levels as âTh2 highâ asthmatics classified using lower airway Th2 gene signature expression. We have identified an 8-gene upper airway signature correlated with lower airway Th2 inflammation, which may be used as a diagnostic biomarker for Th2-driven asthma. Upper airway (nasal) and lower airway (bronchial) epithelial brushings obtained from a cohort of 54 allergic asthmatics and 30 matched healthy controls were profiled by gene expression by microarray. Subjects were assayed for gene expression, serum total IgE, blood eosinophils and serum periostin.
2015-10-23 | E-GEOD-41861 | biostudies-arrayexpress
Project description:Expression data from airway brush biopsy samples, differentiated primary cultures of human airway epithelia, CaLu3 cultures at the air liquid interface, and primary cultures of human airway epithelia submerged in nutrient media Organotypic cultures of primary human airway epithelial cells have been used to investigate the morphology, ion and fluid transport, innate immunity, transcytosis, infection, inflammation, signaling, cilia and repair functions of this complex tissue. However, we do not know how close these cultures resemble the epithelia in vivo. In this study, we examine the genome-wide expression profile of human airway epithelial cells in vivo obtained from brush biopsies of the trachea and bronchus of healthy volunteers and compare it to the expression profile of primary cultures of human airway epithelia grown at the air-liquid interface. For comparison we also investigate the expression profile of Calu3 cells grown at the air-liquid interface and primary cultures of human airway epithelia submerged in nutrient media. We compare the transcriptional profile of human in vivo airway epithelia from trachea and bronchus to differentiated primary human airway epithelia cultures, also from trachea and bronchus, and grown at the air-liquid interface. We also included the profile of Calu3 cultures grown at the air-liquid interface and primary cultures submerged in nutrient media.
2010-04-15 | E-GEOD-20502 | biostudies-arrayexpress
Project description:Cholesterol homeostatic regulator SREBP2 promotes macrophage alternative activation and allergic airway inflammation
| PRJNA778525 | ENA
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:N6-methyladenosine (m6A) modification has been implicated in many cell processes and diseases. YTHDF1, a translation-facilitating m6A reader, is not previously shown to be related to allergic airway inflammation. Here, we report that YTHDF1 is highly expressed in allergic airway epithelial cells (AECs) and asthmatic patients, and influences proinflammatory responses. CLOCK, a subunit of the circadian clock pathway, is the direct target of YTHDF1. YTHDF1 augments CLOCK translation in an m6A-dependent manner. Allergens enhance the liquid‒liquid phase separation (LLPS) of YTHDF1 and drive the formation of a complex comprising dimeric YTHDF1 and CLOCK mRNA, which is distributed to stress granules (SGs). Moreover, YTHDF1 strongly activates NLRP3 inflammasome production and IL-1β secretion, leading to airway inflammatory responses, but these phenotypes are abolished by deleting CLOCK. These findings demonstrate that YTHDF1 is an important regulator of asthmatic airway inflammation, suggesting a potential therapeutic target for allergic airway inflammation.
2024-03-15 | GSE256531 | GEO
Project description:N6-methyladenosine (m6A) modification has been implicated in many cell processes and diseases. YTHDF1, a translation-facilitating m6A reader, is not previously shown to be related to allergic airway inflammation. Here, we report that YTHDF1 is highly expressed in allergic airway epithelial cells (AECs) and asthmatic patients, and influences proinflammatory responses. CLOCK, a subunit of the circadian clock pathway, is the direct target of YTHDF1. YTHDF1 augments CLOCK translation in an m6A-dependent manner. Allergens enhance the liquid‒liquid phase separation (LLPS) of YTHDF1 and drive the formation of a complex comprising dimeric YTHDF1 and CLOCK mRNA, which is distributed to stress granules (SGs). Moreover, YTHDF1 strongly activates NLRP3 inflammasome production and IL-1β secretion, leading to airway inflammatory responses, but these phenotypes are abolished by deleting CLOCK. These findings demonstrate that YTHDF1 is an important regulator of asthmatic airway inflammation, suggesting a potential therapeutic target for allergic airway inflammation.
2024-03-15 | GSE256458 | GEO
Project description:To study modulators of inflammatory airway disease, we developed an in vitro bronchial epithelial cell model system based on the BEAS-2B cell line exposed to lipopolysaccharide (LPS) and diesel exhaust particles (DEP). Combined LPS and DEP exposure triggered a molecular inflammatory phenotype, including elevated TSLP and IL-8 mRNA expression, similar to that observed in airway epithelial cells from asthma patients. In this model, we performed high-throughput perturbation of 24 mRNA and long non-coding (lncRNA) target genes through an arrayed CRISPR-interference screen, followed by shallow RNA-sequencing to identify modulators of inflammation. Perturbation of individual targets had a significant impact on the BEAS-2B DEP/LPS transcriptome. Some mRNA targets reversed the DEP/LPS gene expression signature upon knockdown and could serve as candidate therapeutic targets. Perturbation of other target genes however further amplified the pro-inflammatory signature and thus may have an anti-inflammatory role in these cells. In conclusion, we present a novel in vitro model system for airway inflammation that exhibited an inflammatory profile relevant for asthmatic patients, and demonstrate the feasibility to perform high-throughput target perturbation and molecular phenotyping by integrating CRISPR-interference and shallow RNA-sequencing.
2024-09-15 | GSE271359 | GEO
Project description:Expression data from airway brush biopsy samples, differentiated primary cultures of human airway epithelia, CaLu3 cultures at the air liquid interface, and primary cultures of human airway epithelia submerged in nutrient media Organotypic cultures of primary human airway epithelial cells have been used to investigate the morphology, ion and fluid transport, innate immunity, transcytosis, infection, inflammation, signaling, cilia and repair functions of this complex tissue. However, we do not know how close these cultures resemble the epithelia in vivo. In this study, we examine the genome-wide expression profile of human airway epithelial cells in vivo obtained from brush biopsies of the trachea and bronchus of healthy volunteers and compare it to the expression profile of primary cultures of human airway epithelia grown at the air-liquid interface. For comparison we also investigate the expression profile of Calu3 cells grown at the air-liquid interface and primary cultures of human airway epithelia submerged in nutrient media.
2010-04-15 | GSE20502 | GEO
Project description:Lung epithelial CYP1 activity regulates aryl hydrocarbon receptor dependent allergic airway inflammation
| PRJNA808035 | ENA