The Role of Macrophage Migration Inhibitory Factor (MIF) in Asthmatic Airway Remodeling

• Published in: Allergy, asthma & immunology research Vol. 13; no. 1; pp. 88 - 105
• Main Authors: Li, Ruyi, Wang, Feiyun, Wei, Jianghong, Lin, Yun, Tang, Guofang, Rao, Lizong, Ma, Libing, Xu, Qing, Wu, Jingjie, Lv, Qian, Zhou, Rui, Lei, Huiren, Zhao, Xueqiang, Yao, Dong, Xiao, Bo, Huang, Haiming, Zhang, Jiange, Mo, Biwen
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Academy of Asthma, Allergy and Clinical Immunology 01-01-2021; The Korean Academy of Asthma, Allergy and Clinical Immunology; The Korean Academy of Pediatric Allergy and Respiratory Disease; 대한천식알레르기학회
• Subjects: Animal models; Animal tissues; Antibodies; Asthma; Autophagy; Inflammation; Leukocyte migration; Lungs; Macrophage migration inhibitory factor; Macrophages; Markers; Migration inhibitory factor; Muscles; Original; Ovalbumin; Phagocytosis; Respiratory tract; Smooth muscle; Transfection; Viruses; 내과학; Macrophage migration inhibitory factor; Smooth muscle; autophagy; airway remodeling
• ISSN: 2092-7355; 2092-7363
• DOI: 10.4168/aair.2021.13.1.88

Recent studies have demonstrated that macrophage migration inhibitory factor (MIF) is of importance in asthmatic inflammation. The role of MIF in modulating airway remodeling has not yet been thoroughly elucidated to date. In the present study, we hypothesized that MIF promoted airway remodeling by intensifying airway smooth muscle cell (ASMC) autophagy and explored the specific mechanisms.
MIF knockdown in the lung tissues of C57BL/6 mice was conducted by instilling intratracheally adeno-associated virus (AAV) vectors (MIF-mutant AAV9) into mouse lung tissues. Mice genetically deficient in the autophagy marker ATG5 (ATG5
) was used to detect the role of autophagy in ovalbumin (OVA)-asthmatic murine models. Moreover, to block the expression of MIF and CD74
models, inhibitors, antibodies and lentivirus transfection techniques were employed.
First, MIF knockdown in the lung tissues of mice showed markedly reduced airway remodeling in OVA murine mice models. Secondly, ASMC autophagy was increased in the OVA-challenged models. Mice genetically deficient in the autophagy marker ATG5 (ATG5
) that were primed and challenged with OVA showed lower airway remodeling than genetically wild-type asthmatic mice. Thirdly, MIF can induce ASMC autophagy
. Moreover, the cellular source of MIF which promoted ASMC autophagy was macrophages. Finally, MIF promoted ASMC autophagy in a CD74-dependent manner.
MIF can increase asthmatic airway remodeling by enhancing ASMC autophagy. Macrophage-derived MIF can promote ASMC autophagy by targeting CD74.