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Meteorin-β/Meteorin like/IL-41 attenuates airway inflammation in house dust mite-induced allergic asthma

Cellular & Molecular Immunology volume 19, pages 245–259 (2022)Cite this article

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Abstract

We sought to examine the regulatory effect of Meteorin-β (Metrnβ)/Meteorin like (Metrnl)/IL-41 on lung inflammation in allergic asthma. We found that Metrnβ was elevated significantly in asthmatic patients and in mice with allergic asthma induced by house dust mite (HDM) extract. Upon exposure to HDM, Metrnβ was secreted predominantly by airway epithelial cells and inflammatory cells, including macrophages and eosinophils. The increased Metrnβ effectively blocked the development of airway hyperreactivity (AHR) and decreased inflammatory cell airway infiltration and type 2 cytokine production, which was associated with downregulated DC-mediated adaptive immune responses. Moreover, Metrnβ impaired the maturation and function of bone marrow-derived dendritic cells in vitro. Asthmatic mice adoptively transferred with dendritic cells isolated from Metrnβ-treated allergic mice displayed decreased AHR, airway inflammation, and lung injury. Metrnβ also displayed anti-inflammatory properties in immunodeficient SCID mice with allergic asthma and in in vitro 3D ALI airway models. Moreover, blockade of Metrnβ by anti-Metrnβ antibody treatment promoted the development of allergic asthma. These results revealed the unappreciated protective roles of Metrnβ in alleviating DC-mediated Th2 inflammation in allergic asthma, providing the novel treatment strategy of therapeutic targeting of Metrnβ in allergic asthma.

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Acknowledgements

This research project was supported by a Direct Grant for Research 2021/2022 (Medicine Panel), project code: 2020.011, The Chinese University of Hong Kong, Hong Kong, China. The funders of the study had no involvement in the study design, data collection, data analysis, interpretation, writing of the report, or decision to submit the paper for publication.

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Authors and Affiliations

  1. Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong, China

    Xun Gao, Ellie Jiayi He, Ida Miu-Ting Chu, Miranda Sin-Man Tsang & Chun-Kwok Wong

  2. Department of Paediatrics, The Chinese University of Hong Kong, Hong Kong, China

    Ting-Fan Leung & Gary Wing-Kin Wong

  3. School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China

    Wing-Hung Ko & Mengyun Cai

  4. Emory College of Arts and Sciences, Emory University, Atlanta, GA, USA

    Ellie Jiayi He

  5. Institute of Chinese Medicine and State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants, The Chinese University of Hong Kong, Hong Kong, China

    Miranda Sin-Man Tsang, Ben Chung-Lap Chan, Jiawei Ling & Chun-Kwok Wong

  6. Department of Pathology and Shenzhen Institute of Research and Innovation, The University of Hong Kong, Hong Kong, China

    Xiao Fan & Liwei Lu

  7. Faculty of Medicine and State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau, China

    Christopher Wai-Kei Lam

  8. Li Dak Sum Yip Yio Chin R & D Centre for Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China

    Chun-Kwok Wong

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  1. Xun Gao
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Contributions

XG and C-KW designed the experiments. C-KW obtained the funding. T-FL and GW-KW helped with the clinical experiments. XG, MYC, EJY, IM-TC, MS-MT, BC-LC, JWL, and XF performed the experiments and analyzed the data. XG and C-KW wrote the manuscript. W-HK, CW-KL, and LL revised and edited the manuscript.

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Correspondence to Chun-Kwok Wong.

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Gao, X., Leung, TF., Wong, G.WK. et al. Meteorin-β/Meteorin like/IL-41 attenuates airway inflammation in house dust mite-induced allergic asthma. Cell Mol Immunol 19, 245–259 (2022). https://doi.org/10.1038/s41423-021-00803-8

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