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

Author

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  • Santhoshi V. Akkenepally

    (University of Cincinnati
    National Institute of Nutrition)

  • Dan J. K. Yombo

    (Cincinnati Children’s Hospital Medical Center)

  • Sanjana Yerubandi

    (University of Cincinnati
    Cincinnati Children’s Hospital Medical Center)

  • Geereddy Bhanuprakash Reddy

    (National Institute of Nutrition)

  • Deepak A. Deshpande

    (Sidney Kimmel Medical College, Thomas Jefferson University)

  • Francis X. McCormack

    (University of Cincinnati)

  • Satish K. Madala

    (University of Cincinnati)

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.

Suggested Citation

  • Santhoshi V. Akkenepally & Dan J. K. Yombo & Sanjana Yerubandi & Geereddy Bhanuprakash Reddy & Deepak A. Deshpande & Francis X. McCormack & Satish K. Madala, 2023. "Interleukin 31 receptor α promotes smooth muscle cell contraction and airway hyperresponsiveness in asthma," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-44040-1
    DOI: 10.1038/s41467-023-44040-1
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    References listed on IDEAS

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    1. Ai Kuzumi & Ayumi Yoshizaki & Kazuki M. Matsuda & Hirohito Kotani & Yuta Norimatsu & Maiko Fukayama & Satoshi Ebata & Takemichi Fukasawa & Asako Yoshizaki-Ogawa & Yoshihide Asano & Kyojiro Morikawa & , 2021. "Interleukin-31 promotes fibrosis and T helper 2 polarization in systemic sclerosis," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
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