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

摘要

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 Metrnβwas elevated significantly in asthmatic patients and in mice with allergic asthma induced by house dust mite(HDM)extract.Upon exposure to HDM,Metrnβwas secreted predominantly by airway epithelial cells and inflammatory cells,including macrophages and eosinophils.The increased Metrnβeffectively 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,Metrnβimpaired 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.Metrnβalso displayed anti-inflammatory properties in immunodeficient SCID mice with allergic asthma and in in vitro 3D ALI airway models.Moreover,blockade of Metrnβby anti-Metrnβantibody treatment promoted the development of allergic asthma.These results revealed the unappreciated protective roles of Metrnβin alleviating DC-mediated Th2 inflammation in allergic asthma,providing the novel treatment strategy of therapeutic targeting of Metrnβin allergic asthma.