Dataset Information

Desmoglein-2 dysregulation impairs epithelial barrier integrity in eosinophilic asthma.

ABSTRACT:

SUBMITTER: Yao L

PROVIDER: S-EPMC12908299 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature

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Desmoglein-2 dysregulation impairs epithelial barrier integrity in eosinophilic asthma.

Yao Lei L Yuan Xijing X Sun Peng P Fu Heng H Kermani Nazanin Zounemat NZ Adcock Ian M IM Liu Yi Y Jia Man M Yao Xin X

Respiratory research 20260121 1

BACKGROUND: Eosinophilic asthma, affecting more than 50% of adult asthma patients, demonstrates airway inflammation severity directly correlated with eosinophil infiltration levels. While transepithelial eosinophil migration constitutes a pivotal step in airway inflammation pathogenesis, the regulatory mechanisms remain undefined. We aim to investigate how desmoglein-2 (DSG2), which is a key desmosomal cadherin mediating epithelial intercellular adhesion, regulates eosinophil transmigration acro ...[more]

PMID: 41566510

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Project description:Asthma is a complex, chronic respiratory disease with marked clinical and pathophysiological heterogeneity. Distinct inflammatory phenotypes of eosinophilic, mixed, neutrophilic and paucigranulocytic asthma are identified in patients, but most in vivo mouse models, studying asthma mechanisms, mimic only eosinophilic phenotype in humans. The detailed unbiased in vivo studies on molecular responses among different kinds of inflammation in asthma models are lacking. Therefore, we developed mouse models representing three different inflammatory phenotypes of airway inflammation, namely eosinophilic, mixed, and neutrophilic asthma via different methods of house dust mite sensitisation. We used microarrays to determine the global gene expression in the lungs of mice with eosinophilic, mixed and neutrophilic inflammatory phenotypes to uncover underlying differences in clinical presentation and to find novel molecular targets and pathways, which might reflect different molecular mechanisms of the disease. By whole genome transcriptome profiling, we found that airway tight junction (TJ) molecules, mucins and inflammasome-related genes are differentially expressed in distinct phenotypes of allergic airway inflammation. Next, detailed analysis of several molecules from these families by quantitative RT-PCR, western blot and confocal microscopy revealed that (i) Zo-1 and Cldn18 were downregulated in all phenotypes, while Cldn4 upregulation was characteristic for neutrophilic airway inflammation; (ii) mucins Clca1 (Gob5) and Muc5ac were upregulated in eosinophilic and even more in neutrophilic asthma, and (iii) upregulation of inflammasome-related molecules such as Nlrp3, Nlrc4, Casp-1 and IL-1b was characteristic for neutrophilic asthma. Finally, we showed that inflammasome/Th-17/neutrophilic axis cytokines, namely IL-1b and IL-17 impaired epithelial barrier function and increased mucins expressions in primary human bronchial epithelial cells from normal and asthmatic donors. Our findings suggest that differential expression of TJs, mucins and inflammasome-related molecules in distinct asthma phenotypes could be mechanistically linked and might further reflect the differences observed in the clinic.

Dataset Information

Desmoglein-2 dysregulation impairs epithelial barrier integrity in eosinophilic asthma.

Publications

Desmoglein-2 dysregulation impairs epithelial barrier integrity in eosinophilic asthma.

Similar Datasets

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