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Cullin5 drives experimental asthma exacerbations by modulating alveolar macrophage antiviral immunity
- Source :
- Nature Communications, Vol 15, Iss 1, Pp 1-19 (2024)
- Publication Year :
- 2024
- Publisher :
- Nature Portfolio, 2024.
-
Abstract
- Abstract Asthma exacerbations caused by respiratory viral infections are a serious global health problem. Impaired antiviral immunity is thought to contribute to the pathogenesis, but the underlying mechanisms remain understudied. Here using mouse models we find that Cullin5 (CUL5), a key component of Cullin-RING E3 ubiquitin ligase 5, is upregulated and associated with increased neutrophil count and influenza-induced exacerbations of house dust mite-induced asthma. By contrast, CUL5 deficiency mitigates neutrophilic lung inflammation and asthma exacerbations by augmenting IFN-β production. Mechanistically, following thymic stromal lymphopoietin stimulation, CUL5 interacts with O-GlcNAc transferase (OGT) and induces Lys48-linked polyubiquitination of OGT, blocking the effect of OGT on mitochondrial antiviral-signaling protein O-GlcNAcylation and RIG-I signaling activation. Our results thus suggest that, in mouse models, pre-existing allergic injury induces CUL5 expression, impairing antiviral immunity and promoting neutrophilic inflammation for asthma exacerbations. Targeting of the CUL5/IFN-β signaling axis may thereby serve as a possible therapy for treating asthma exacerbations.
- Subjects :
- Science
Subjects
Details
- Language :
- English
- ISSN :
- 20411723 and 25631551
- Volume :
- 15
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Nature Communications
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.25631551068045989c561b0d3d724983
- Document Type :
- article
- Full Text :
- https://doi.org/10.1038/s41467-023-44168-0