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Jakwerth, C.A. ; Chaker, A. ; Guerth, F. ; Oelsner, M. ; Pechtold, L. ; zur Bonsen, L.S. ; Ullmann, J.T. ; Krauss-Etschmann, S.* ; Erb, A. ; Kau, J. ; Plaschke, M. ; Winkler, M. ; Kurz, A. ; Kloss, A. ; Esser-von Bieren, J. ; Schmidt-Weber, C.B. ; Zissler, U.M.

Sputum microRNA-screening reveals Prostaglandin EP3 receptor as selective target in allergen-specific immunotherapy.

Clin. Exp. Allergy, DOI: 10.1111/cea.14013 (2021)
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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 of 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 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: 259 miRs were upregulated in the sputum of AA patients compared to 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 to 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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Allergen-specific Immunotherapy ; Allergic Asthma/rhinitis ; Induced Sputum ; Microrna ; Prostaglandin E2
Language english
Publication Year 2021
HGF-reported in Year 2021
ISSN (print) / ISBN 0954-7894
e-ISSN 1365-2222
Journal Clinical & Experimental Allergy
Publisher Wiley
Publishing Place 111 River St, Hoboken 07030-5774, Nj Usa
Reviewing status Peer reviewed
Institute(s) Institute for Allergy Research (IAF)
POF-Topic(s) 30202 - Environmental Health
Research field(s) Allergy
PSP Element(s) G-505400-001
G-554600-001
Grants German Research Foundation (DFG)
Comprehensive Pneumology Center (CPC) Munich
German Center for Lung Research (DZL)
DOI 10.1111/cea.14013
WOS ID WOS:000700039300001
Scopus ID 85115331000
PubMed ID 34514658
Erfassungsdatum 2021-10-19
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