Local glucocorticoid synthesis regulates house dust mite-induced airway hypersensitivity in mice

Merk, VM, Phan, TS, Wiedmann, A, Hardy, RS, Lavery, GG ORCID: https://orcid.org/0000-0001-5794-748X and Brunner, T, 2023. Local glucocorticoid synthesis regulates house dust mite-induced airway hypersensitivity in mice. Frontiers in Immunology, 14: 1252874. ISSN 1664-3224

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Abstract

Background: Extra-adrenal glucocorticoid (GC) synthesis at epithelial barriers, such as skin and intestine, has been shown to be important in the local regulation of inflammation. However, the role of local GC synthesis in the lung is less well studied. Based on previous studies and the uncontentious efficacy of corticosteroid therapy in asthma patients, we here investigated the role of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1/Hsd11b1)-dependent local GC reactivation in the regulation of allergic airway inflammation.

Methods: Airway inflammation in Hsd11b1-deficient and C57BL/6 wild type mice was analyzed after injection of lipopolysaccharide (LPS) and anti-CD3 antibody, and in acute and chronic models of airway hypersensitivity induced by house dust mite (HDM) extract. The role of 11β-HSD1 in normal and inflammatory conditions was assessed by high dimensional flow cytometry, histological staining, RT-qPCR analysis, ex vivo tissue cultures, GC-bioassays and protein detection by ELISA and immunoblotting.

Results: Here we show that lung tissue from Hsd11b1-deficient mice synthesized significantly less GC ex vivo compared with wild type animals in response to immune cell stimulation. We further observed a drastically aggravated phenotype in Hsd11b1-deficient mice treated with HDM extract compared to wild type animals. Besides eosinophilic infiltration, Hsd11b1-deficient mice exhibited aggravated neutrophilic infiltration caused by a strong Th17-type immune response.

Conclusion: We propose an important role of 11β-HSD1 and local GC in regulating Th17-type rather than Th2-type immune responses in HDM-induced airway hypersensitivity in mice by potentially controlling Toll-like receptor 4 (TLR4) signaling and cytokine/chemokine secretion by airway epithelial cells.

Item Type:	Journal article
Publication Title:	Frontiers in Immunology
Creators:	Merk, V.M., Phan, T.S., Wiedmann, A., Hardy, R.S., Lavery, G.G. and Brunner, T.
Publisher:	Frontiers Media SA
Date:	2023
Volume:	14
ISSN:	1664-3224
Identifiers:	Number Type 10.3389/fimmu.2023.1252874 DOI 2554413 Other
Rights:	© 2023 Merk, Phan, Wiedmann, Hardy, Lavery and Brunner. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (http://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Divisions:	Schools > School of Science and Technology
Record created by:	Laura Borcherds
Date Added:	09 Jan 2026 09:45
Last Modified:	09 Jan 2026 09:45
URI:	https://irep.ntu.ac.uk/id/eprint/54997

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