Macrophage migration inhibitory factor (MIF), a pleiotropic cytokine, is expressed in various cell types including hematopoietic, epithelial, etc. It has upstream regulatory roles in innate and adaptive immunity, and is involved in multiple signaling pathways such as ERK1/2, AMPK and AKT upon binding to receptors like CD74/CD44, CXCR2, CXCR4 and CXCR7 [1,2]. MIF is crucial for numerous physiological processes and is also associated with a multitude of diseases [1,3].

Genetic depletion of myeloid-derived MIF in perioperative ischemic stroke mice leads to a significant reduction in endothelial cell apoptosis and necroptosis and the associated blood-brain barrier disruption, indicating its role in promoting cell death in ischemic brain injury [4]. In mouse models of allergic asthma, the lack of MIF almost completely abrogates mucus secretion, eosinophilic inflammation, and airway hyper-responsiveness, showing its importance in type-2-mediated inflammation [5].

In conclusion, MIF is essential in immune responses and physiological processes. Through gene knockout studies in mouse models, its role in diseases such as ischemic brain injury and allergic asthma has been revealed. These findings contribute to understanding the pathogenesis of these diseases and may provide new therapeutic targets.

References:

1. Jankauskas, Stanislovas S, Wong, Dickson W L, Bucala, Richard, Djudjaj, Sonja, Boor, Peter. 2019. Evolving complexity of MIF signaling. In Cellular signalling, 57, 76-88. doi:10.1016/j.cellsig.2019.01.006. https://pubmed.ncbi.nlm.nih.gov/30682543/

2. Bilsborrow, Joshua B, Doherty, Edward, Tilstam, Pathricia V, Bucala, Richard. 2019. Macrophage migration inhibitory factor (MIF) as a therapeutic target for rheumatoid arthritis and systemic lupus erythematosus. In Expert opinion on therapeutic targets, 23, 733-744. doi:10.1080/14728222.2019.1656718. https://pubmed.ncbi.nlm.nih.gov/31414920/

3. Sumaiya, Krishnamoorthi, Langford, Dianne, Natarajaseenivasan, Kalimuthusamy, Shanmughapriya, Santhanam. 2021. Macrophage migration inhibitory factor (MIF): A multifaceted cytokine regulated by genetic and physiological strategies. In Pharmacology & therapeutics, 233, 108024. doi:10.1016/j.pharmthera.2021.108024. https://pubmed.ncbi.nlm.nih.gov/34673115/

4. Li, Yan, Zou, Chengyu, Chen, Chen, Yuan, Junying, Li, Peiying. 2023. Myeloid-derived MIF drives RIPK1-mediated cerebromicrovascular endothelial cell death to exacerbate ischemic brain injury. In Proceedings of the National Academy of Sciences of the United States of America, 120, e2219091120. doi:10.1073/pnas.2219091120. https://pubmed.ncbi.nlm.nih.gov/36693098/

5. Bozza, Marcelo T, Lintomen, Leticia, Kitoko, Jamil Z, Paiva, Cláudia N, Olsen, Priscilla C. . The Role of MIF on Eosinophil Biology and Eosinophilic Inflammation. In Clinical reviews in allergy & immunology, 58, 15-24. doi:10.1007/s12016-019-08726-z. https://pubmed.ncbi.nlm.nih.gov/30680604/