First Author | Akkenepally SV | Year | 2023 |
Journal | Nat Commun | Volume | 14 |
Issue | 1 | Pages | 8207 |
PubMed ID | 38081868 | Mgi Jnum | J:343731 |
Mgi Id | MGI:7566747 | Doi | 10.1038/s41467-023-44040-1 |
Citation | Akkenepally SV, et al. (2023) Interleukin 31 receptor alpha promotes smooth muscle cell contraction and airway hyperresponsiveness in asthma. Nat Commun 14(1):8207 |
abstractText | Asthma is a chronic inflammatory airway disease characterized by airway hyperresponsiveness (AHR), inflammation, and goblet cell hyperplasia. Multiple cytokines, including IFNgamma, IL-4, and IL-13 are associated with asthma; however, the mechanisms underlying the effects of these cytokines remain unclear. Here, we report a significant increase in the expression of IL-31RA, but not its cognate ligand IL-31, in mouse models of allergic asthma. In support of this, IFNgamma, IL-4, and IL-13 upregulated IL-31RA but not IL-31 in both human and mice primary airway smooth muscle cells (ASMC) isolated from the airways of murine and human lungs. Importantly, the loss of IL-31RA attenuated AHR but had no effect on inflammation and goblet cell hyperplasia in mice challenged with allergens or treated with IL-13 or IFNgamma. We show that IL-31RA functions as a positive regulator of muscarinic acetylcholine receptor 3 expression, augmenting calcium levels and myosin light chain phosphorylation in human and murine ASMC. These findings identify a role for IL-31RA in AHR that is distinct from airway inflammation and goblet cell hyperplasia in asthma. |