Airway Epithelial Cells Are Crucial Targets of Glucocorticoids in a Mouse Model of Allergic Asthma

The Journal of Immunology : Official Journal of the American Association of Immunologists
Carina KlaßenH M Reichardt

Abstract

Although glucocorticoids (GCs) are a mainstay in the clinical management of asthma, the target cells that mediate their therapeutic effects are unknown. Contrary to our expectation, we found that GC receptor (GR) expression in immune cells was dispensable for successful therapy of allergic airway inflammation (AAI) with dexamethasone. Instead, GC treatment was compromised in mice expressing a defective GR in the nonhematopoietic compartment or selectively lacking the GR in airway epithelial cells. Further, we found that an intact GR dimerization interface was a prerequisite for the suppression of AAI and airway hyperresponsiveness by GCs. Our observation that the ability of dexamethasone to modulate gene expression in airway epithelial cells coincided with its potency to resolve AAI supports a crucial role for transcriptional regulation by the GR in this cell type. Taken together, we identified an unknown mode of GC action in the treatment of allergic asthma that might help to develop more specific therapies in the future.

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Citations

Aug 25, 2017·International Journal of Molecular Sciences·Fred Lühder, Holger M Reichardt
Nov 11, 2017·International Journal of Molecular Sciences·Anca D PetrescuSharon DeMorrow
Aug 10, 2019·Frontiers in Immunology·Cindy StrehlFrank Buttgereit
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Sep 2, 2020·Cellular & Molecular Immunology·Linda Quatrini, Sophie Ugolini
Sep 26, 2020·Frontiers in Bioengineering and Biotechnology·Barbara DraslerBarbara Rothen-Rutishauser
Nov 22, 2020·Seminars in Immunopathology·Akihiro Shimba, Koichi Ikuta
Jan 8, 2021·The Journal of Biological Chemistry·Mahmoud M MostafaRobert Newton
Feb 13, 2021·Frontiers in Immunology·Drishti Tiwari, Pawan Gupta
Nov 14, 2020·The Journal of Biological Chemistry·Mahmoud M MostafaRobert Newton
Mar 2, 2021·Frontiers in Immunology·Beatriz León, Andre Ballesteros-Tato
Dec 15, 2020·Cellular and Molecular Gastroenterology and Hepatology·Chiara MuzziSybille D Reichardt

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