期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 53, 期 6, 页码 -出版社
WILEY
DOI: 10.1002/eji.202250016
关键词
allergic asthma; eosinophils; macrophage migration inhibitory factor; house dust mite
类别
Macrophage migration inhibitory factor (MIF) is highly expressed in BALF and serum of asthmatic patients and contributes to asthmatic pathogenesis in mice. This study investigated the role of MIF in a more complex and relevant asthma model using house dust mite (HDM) extract. Results showed that MIF deficiency reduced airway hyperresponsiveness, eosinophil infiltration, mucus hypersecretion, and subepithelial fibrosis in HDM-challenged mice. Additionally, MIF blockade prevented the increase of inflammatory cytokines IL-4, IL-5, and IL-13 in the lungs while preserving CCL11 levels. These findings suggest that MIF may be a promising target for asthma therapy.
Macrophage migration inhibitory factor (MIF) is present in high amounts in the BALF and serum of asthmatic patients, contributing to the pathogenesis of experimental asthma induced by OVA in mice. Whether MIF contributes to the physiopathology on a more complex and relevant asthma model has not been characterized. Mif-deficient (Mif(-/-)) or WT mice treated with anti-MIF antibody were challenged multiple times using house dust mite (HDM) extract by the intranasal route. HDM-challenged Mif(-/-) mice presented decreased airway hyperresponsiveness, lung infiltration of eosinophils, mucus hypersecretion, and subepithelial fibrosis compared to HDM-challenged WT mice. Amounts of IL-4, IL-5, and IL-13 were decreased in the lungs of Mif(-/-) mice upon HDM challenges, but the increase of CCL11 was preserved, compared to HDM-challenged WT mice. We also observed increased numbers of group 2 innate lymphoid cells and Th2 cells in the BALF and mediastinal LNs (mLN)-induced challenged by HDM of WT mice, but not in HDM-challenged Mif(-/-) mice. Anti-MIF treatment abrogated the airway infiltration of eosinophils, mucus hypersecretion, and subepithelial fibrosis in the lungs of HDM-challenged mice. In conclusion, MIF ablation prevents the pathologic hallmarks of asthma in HDM-challenged mice, reinforcing the promising target of MIF for asthma therapy.
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