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| Verfasst von: | Hey, Joschka [VerfasserIn]  |
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| | Paulsen, Michelle [VerfasserIn] |
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| | Toth, Reka [VerfasserIn] |
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| | Weichenhan, Dieter [VerfasserIn] |
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| | Butz, Simone [VerfasserIn] |
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| | Schatterny, Jolanthe [VerfasserIn] |
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| | Liebers, Reinhard [VerfasserIn] |
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| | Lutsik, Pavlo [VerfasserIn] |
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| | Plass, Christoph [VerfasserIn] |
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| | Mall, Marcus A. [VerfasserIn] |
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| Titel: | Epigenetic reprogramming of airway macrophages promotes polarization and inflammation in muco-obstructive lung disease |
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| Verf.angabe: | Joschka Hey, Michelle Paulsen, Reka Toth, Dieter Weichenhan, Simone Butz, Jolanthe Schatterny, Reinhard Liebers, Pavlo Lutsik, Christoph Plass, Marcus A. Mall |
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| E-Jahr: | 2021 |
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| Jahr: | 11 November 2021 |
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| Umfang: | 18 S. |
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| Fussnoten: | Gesehen am 12.11.2021 |
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| Titel Quelle: | Enthalten in: Nature Communications |
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| Ort Quelle: | [London] : Nature Publishing Group UK, 2010 |
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| Jahr Quelle: | 2021 |
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| Band/Heft Quelle: | 12(2021), Artikel-ID 6520, Seite 1-18 |
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| ISSN Quelle: | 2041-1723 |
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| Abstract: | Lung diseases, such as cystic fibrosis and COPD, are characterized by mucus obstruction and chronic airway inflammation, but their mechanistic link remains poorly understood. Here, we focus on the function of the mucostatic airway microenvironment on epigenetic reprogramming of airway macrophages (AM) and resulting transcriptomic and phenotypical changes. Using a mouse model of muco-obstructive lung disease (Scnn1b-transgenic), we identify epigenetically controlled, differentially regulated pathways and transcription factors involved in inflammatory responses and macrophage polarization. Functionally, AMs from Scnn1b-transgenic mice have reduced efferocytosis and phagocytosis, and excessive inflammatory responses upon lipopolysaccharide challenge, mediated through enhanced Irf1 function and expression. Ex vivo stimulation of wild-type AMs with native mucus impairs efferocytosis and phagocytosis capacities. In addition, mucus induces gene expression changes, comparable with those observed in AMs from Scnn1b-transgenic mice. Our data show that mucostasis induces epigenetic reprogramming of AMs, leading to changes favoring tissue damage and disease progression. Targeting these altered AMs may support therapeutic approaches in patients with muco-obstructive lung diseases. |
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| DOI: | doi:10.1038/s41467-021-26777-9 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext ; Verlag: https://doi.org/10.1038/s41467-021-26777-9 |
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| | Volltext: https://www.nature.com/articles/s41467-021-26777-9 |
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| | DOI: https://doi.org/10.1038/s41467-021-26777-9 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | Alveolar macrophages |
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| | Chronic obstructive pulmonary disease |
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| | Cystic fibrosis |
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| | Epigenetics |
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| K10plus-PPN: | 1777366712 |
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| Verknüpfungen: | → Zeitschrift |
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Epigenetic reprogramming of airway macrophages promotes polarization and inflammation in muco-obstructive lung disease / Hey, Joschka [VerfasserIn]; 11 November 2021 (Online-Ressource)
