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Published on: May 30, 2020
Meteorin-β/Meteorin like/IL-41 attenuates airway inflammation in house dust mite-induced allergic asthma
Xun Gao1, Ting-Fan Leung2, Gary Wing-Kin Wong2
1Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong, China.
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.
Insights
Meteorin-β (Metrnβ) protects against allergic asthma by reducing lung inflammation and airway hyperreactivity. This protein dampens immune responses, offering a potential new therapeutic target for asthma.
Area of Science:
- Immunology
- Pulmonology
- Molecular Biology
Background:
- Allergic asthma is characterized by airway inflammation and hyperreactivity.
- The role of Meteorin-β (Metrnβ) in allergic asthma pathogenesis is not well understood.
Purpose of the Study:
- To investigate the regulatory effects of Meteorin-β (Metrnβ) on lung inflammation in allergic asthma.
- To explore Metrnβ as a potential therapeutic target for allergic asthma.
Main Methods:
- Quantification of Metrnβ levels in asthmatic patients and house dust mite (HDM)-induced mouse models.
- Analysis of Metrnβ secretion by airway cells and inflammatory cells.
- In vitro studies on dendritic cell (DC) maturation and function.
- Adoptive transfer experiments with Metrnβ-treated DCs.
- Assessment of anti-inflammatory effects in immunodeficient mice and 3D airway models.
- In vivo blockade of Metrnβ using antibodies.
Main Results:
- Metrnβ levels were significantly elevated in asthmatic patients and mice.
- Metrnβ inhibited airway hyperreactivity, reduced inflammatory cell infiltration, and decreased type 2 cytokine production.
- Metrnβ impaired dendritic cell maturation and function, leading to downregulated adaptive immune responses.
- Adoptive transfer of Metrnβ-treated DCs reduced asthma severity.
- Blocking Metrnβ exacerbated allergic asthma development.
Conclusions:
- Meteorin-β (Metrnβ) plays a protective role in allergic asthma by mitigating DC-mediated Th2 inflammation.
- Targeting Metrnβ represents a novel therapeutic strategy for allergic asthma.
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