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Sputum microRNA-screening reveals Prostaglandin EP3 receptor as selective target in allergen-specific immunotherapy.
Jakwerth, Constanze A; Chaker, Adam M; Guerth, Ferdinand; Oelsner, Madlen; Pechtold, Lisa; Zur Bonsen, Lynn S; Ullmann, Julia T; Krauss-Etschmann, Susanne; Erb, Anna; Kau, Josephine; Plaschke, Mirjam; Winkler, Marlene; Kurz, Alexandra; Kloss, Antonia; Esser-von Bieren, Julia; Schmidt-Weber, Carsten B; Zissler, Ulrich M.
Afiliación
  • Jakwerth CA; Center 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.
  • Chaker AM; Center 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.
  • Guerth F; Department of Otorhinolaryngology, TUM School of Medicine, Technical University Munich, Klinikum rechts der Isar, Munich, Germany.
  • Oelsner M; Center 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.
  • Pechtold L; Center 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.
  • Zur Bonsen LS; Center 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.
  • Ullmann JT; Department of Otorhinolaryngology, TUM School of Medicine, Technical University Munich, Klinikum rechts der Isar, Munich, Germany.
  • Krauss-Etschmann S; Center 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.
  • Erb A; Department of Otorhinolaryngology, TUM School of Medicine, Technical University Munich, Klinikum rechts der Isar, Munich, Germany.
  • Kau J; Center 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.
  • Plaschke M; Research Center Borstel, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Borstel, Germany.
  • Winkler M; Institute of Experimental Medicine, Christian-Albrechts University Kiel, Kiel, Germany.
  • Kurz A; Center 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.
  • Kloss A; Center 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.
  • Esser-von Bieren J; Department of Otorhinolaryngology, TUM School of Medicine, Technical University Munich, Klinikum rechts der Isar, Munich, Germany.
  • Schmidt-Weber CB; Center 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.
  • Zissler UM; Department of Otorhinolaryngology, TUM School of Medicine, Technical University Munich, Klinikum rechts der Isar, Munich, Germany.
Clin Exp Allergy ; 51(12): 1577-1591, 2021 12.
Article en En | MEDLINE | ID: mdl-34514658
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: MicroARNs / Rinitis Alérgica Tipo de estudio: Diagnostic_studies / Screening_studies Límite: Humans Idioma: En Revista: Clin Exp Allergy Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2021 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: MicroARNs / Rinitis Alérgica Tipo de estudio: Diagnostic_studies / Screening_studies Límite: Humans Idioma: En Revista: Clin Exp Allergy Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2021 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido