| First Author | Zhang H | Year | 2024 |
| Journal | Nat Commun | Volume | 15 |
| Issue | 1 | Pages | 252 |
| PubMed ID | 38177117 | Mgi Jnum | J:346009 |
| Mgi Id | MGI:7571953 | Doi | 10.1038/s41467-023-44168-0 |
| Citation | Zhang H, et al. (2024) Cullin5 drives experimental asthma exacerbations by modulating alveolar macrophage antiviral immunity. Nat Commun 15(1):252 |
| abstractText | 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-beta 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-beta signaling axis may thereby serve as a possible therapy for treating asthma exacerbations. |
