Interleukin 31 receptor α promotes smooth muscle cell contraction and airway hyperresponsiveness in asthma

Nat Commun. 2023 Dec 11;14(1):8207. doi: 10.1038/s41467-023-44040-1.

Abstract

Asthma is a chronic inflammatory airway disease characterized by airway hyperresponsiveness (AHR), inflammation, and goblet cell hyperplasia. Multiple cytokines, including IFNγ, 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, IFNγ, 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 IFNγ. 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.

MeSH terms

  • Animals
  • Asthma* / genetics
  • Asthma* / metabolism
  • Cytokines / metabolism
  • Disease Models, Animal
  • Humans
  • Hyperplasia / metabolism
  • Inflammation / metabolism
  • Interleukin-13 / metabolism
  • Interleukin-4 / metabolism
  • Interleukins / genetics
  • Interleukins / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Myocytes, Smooth Muscle / metabolism
  • Respiratory Hypersensitivity* / metabolism

Substances

  • Cytokines
  • Interleukin-13
  • Interleukin-4
  • Interleukins
  • IL31RA protein, human
  • Il31ra protein, mouse