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

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