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Updated: Oct 20, 2025
Murine Model of Allergen Induced Asthma
Published on: May 14, 2012
Sputum microRNA-screening reveals Prostaglandin EP3 receptor as selective target in allergen-specific immunotherapy
Constanze A Jakwerth1, Adam M Chaker1,2, Ferdinand Guerth1
1Center of Allergy & Environment (ZAUM), Technical University of Munich (TUM), Helmholtz Center Munich, German Research Center for Environmental Health, Member of the German Center for Lung Research (DZL), CPC-M, Munich, Germany.
Background:
Several microRNAs (miRs) have been described as potential biomarkers in liquid biopsies and in the context of allergic asthma, while therapeutic effects on the airway expression of miRs remain elusive. In this study, we investigated epigenetic miR-associated mechanisms in the sputum of grass pollen-allergic patients with and without allergen-specific immunotherapy (AIT).
Methods:
Induced sputum samples of healthy controls (HC), AIT-treated and -untreated grass pollen-allergic rhinitis patients with (AA) and without asthma (AR) were profiled using miR microarray and whole-transcriptome microarray analysis of the same samples. miR targets were predicted in silico and used to identify inverse regulation. Local PGE2 levels were measured using ELISA.
Results:
Two hundred and fifty nine miRs were upregulated in the sputum of AA patients compared with HC, while only one was downregulated. The inverse picture was observed in induced sputum of AIT-treated patients: while 21 miRs were downregulated, only 4 miRs were upregulated in asthmatics upon AIT. Of these 4 miRs, miR-3935 stood out, as its predicted target PTGER3, the prostaglandin EP3 receptor, was downregulated in treated AA patients compared with untreated. The levels of its ligand PGE2 in the sputum supernatants of these samples were increased in allergic patients, especially asthmatics, and downregulated after AIT. Finally, local PGE2 levels correlated with ILC2 frequencies, secreted sputum IL-13 levels, inflammatory cell load, sputum eosinophils and symptom burden.
Conclusions:
While profiling the sputum of allergic patients for novel miR expression patterns, we uncovered an association between miR-3935 and its predicted target gene, the prostaglandin E3 receptor, which might mediate AIT effects through suppression of the PGE2 -PTGER3 axis.
Insights
Allergen-specific immunotherapy (AIT) impacts microRNA (miR) expression in allergic asthma patients. miR-3935 may mediate AIT effects by regulating prostaglandin E2 (PGE2) and its receptor, offering therapeutic insights.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRs) are potential biomarkers in liquid biopsies for allergic asthma.
- Therapeutic effects of microRNAs on airway gene expression are not well understood.
- This study investigates microRNA-associated epigenetic mechanisms in allergic asthma patients undergoing immunotherapy.
Purpose of the Study:
- To explore microRNA expression patterns in the sputum of grass pollen-allergic patients.
- To investigate the role of microRNAs in allergen-specific immunotherapy (AIT).
- To identify potential microRNA-mediated therapeutic mechanisms in allergic asthma.
Main Methods:
- Induced sputum samples from healthy controls, AIT-treated, and untreated allergic rhinitis and asthma patients were analyzed.
- MicroRNA (miR) and whole-transcriptome microarray analyses were performed on the same samples.
- In silico prediction of miR targets, ELISA for prostaglandin E2 (PGE2) levels, and correlation analyses were conducted.
Main Results:
- Two hundred fifty-nine miRs were upregulated in allergic asthma patients compared to healthy controls.
- AIT treatment led to inverse microRNA expression changes, with 21 miRs downregulated in asthmatics.
- miR-3935 was identified as a key microRNA, inversely correlated with its target PTGER3 and linked to PGE2 levels, which decreased post-AIT.
Conclusions:
- A novel association between miR-3935 and its target, the prostaglandin E3 receptor (PTGER3), was discovered.
- This interaction may play a role in mediating AIT effects via the PGE2-PTGER3 axis.
- Findings suggest a potential microRNA-based therapeutic strategy for allergic asthma.
