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 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.

Highly Selective MIF Ketonase Inhibitor KRP-6 Diminishes M1 Macrophage Polarization and Metabolic Reprogramming

“…Many different enzyme activities of MIF have been discovered thus far, such as endonuclease [34] or the thiol-protein oxidoreductase [35]. MIF was recently implicated in the pathogenesis of several chronic inflammatory and autoimmune disease including asthma [36,37], rheumatoid arthritis, systemic lupus erythematosus [38], spinal cord injuries [39] or Hashimoto's thyroiditis [40]. Eosinophils and neutrophils are multifunctional cells which not only contribute to first line host defense against infections, but also to initiation, modulation and resolution of inflammation, thus serving as critical effectors during inflammatory and autoimmune diseases.…”