MIF is essential to the establishment of house dust mite-induced airway inflammation and tissue remodeling in mice.

Abstract

Macrophage migration inhibitory factor (MIF) is present in high amounts in the bronchoalveolar lavage fluid (BALF) and serum of asthmatic patients contributing to the pathogenesis of experimental asthma induced by ovalbumin (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 wild-type (WT) mice treated with anti-MIF antibody were challenged multiple times using house dust mite (HDM) extract by 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 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 lymph nodes (mLN) induced challenged by HDM of WT mice, but not in HDM-challenged Mif-/- mice. Anti-MIF treatment abrogated the airways 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. This article is protected by copyright. All rights reserved.