Macrophage-intrinsic DUOX1 contributes to type 2 inflammation and mucus metaplasia during allergic airway disease.

Autor: Morris CR; Department of Pathology and Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, USA., Habibovic A; Department of Pathology and Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, USA., Dustin CM; Department of Pathology and Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, USA., Schiffers C; Department of Pathology and Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, USA., Lin MC; Department of Pathology and Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, USA., Ather JL; Department of Medicine, Larner College of Medicine, University of Vermont, Burlington, VT, USA., Janssen-Heininger YMW; Department of Pathology and Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, USA., Poynter ME; Department of Medicine, Larner College of Medicine, University of Vermont, Burlington, VT, USA., Utermohlen O; Institute for Medical Microbiology, Immunology and Hygiene, University Hospital Cologne, Cologne, Germany., Krönke M; Institute for Medical Microbiology, Immunology and Hygiene, University Hospital Cologne, Cologne, Germany., van der Vliet A; Department of Pathology and Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, USA. albert.van-der-vliet@uvm.edu.
Jazyk: angličtina
Zdroj: Mucosal immunology [Mucosal Immunol] 2022 May; Vol. 15 (5), pp. 977-989. Date of Electronic Publication: 2022 Jun 02.
DOI: 10.1038/s41385-022-00530-x
Abstrakt: The NADPH oxidase DUOX1 contributes to epithelial production of alarmins, including interleukin (IL)-33, in response to injurious triggers such as airborne protease allergens, and mediates development of mucus metaplasia and airway remodeling in chronic allergic airways diseases. DUOX1 is also expressed in non-epithelial lung cell types, including macrophages that play an important role in airway remodeling during chronic lung disease. We therefore conditionally deleted DUOX1 in either lung epithelial or monocyte/macrophage lineages to address its cell-specific actions in innate airway responses to acute airway challenge with house dust mite (HDM) allergen, and in chronic HDM-driven allergic airway inflammation. As expected, acute responses to airway challenge with HDM, as well as type 2 inflammation and related features of airway remodeling during chronic HDM-induced allergic inflammation, were largely driven by DUOX1 with the respiratory epithelium. However, in the context of chronic HDM-driven inflammation, DUOX1 deletion in macrophages also significantly impaired type 2 cytokine production and indices of mucus metaplasia. Further studies revealed a contribution of macrophage-intrinsic DUOX1 in macrophage recruitment upon chronic HDM challenge, as well as features of macrophage activation that impact on type 2 inflammation and remodeling.
(© 2022. The Author(s), under exclusive licence to Society for Mucosal Immunology.)
Databáze: MEDLINE
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