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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)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Allergen-specific Immunotherapy ; Allergic Asthma/rhinitis ; Induced Sputum ; Microrna ; Prostaglandin E2
ISSN (print) / ISBN 0954-7894
e-ISSN 1365-2222
Zeitschrift Clinical & Experimental Allergy
Verlag Wiley
Verlagsort 111 River St, Hoboken 07030-5774, Nj Usa
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute for Allergy Research (IAF)
Förderungen German Research Foundation (DFG)
Comprehensive Pneumology Center (CPC) Munich
German Center for Lung Research (DZL)