Mif-flox Mouse

Macrophage migration inhibitory factor (MIF) is a pleiotropic pro-inflammatory cytokine. It was initially identified as a cytokine from activated T cells and is now known to be secreted by various cell types such as hematopoietic, epithelial, endothelial, mesenchymal, and neuronal cells [2,3]. MIF plays a critical role in innate and adaptive immunity, cell survival signaling, and can regulate glucocorticoid-mediated immunosuppression [1,3]. It acts via binding to receptors like CD74/CD44, CXCR2, CXCR4, and CXCR7, activating downstream pathways including ERK1/2, AMPK, and AKT [2].

In pre-clinical models, genetic depletion of myeloid-derived MIF in perioperative ischemic stroke mice with middle cerebral artery occlusion following a surgical insult led to a significant reduction in endothelial cell apoptosis and necroptosis, as well as blood-brain-barrier disruption [4]. In mouse models of allergic asthma, the lack of MIF caused an almost complete abrogation of mucus secretion, eosinophilic inflammation, and airway hyper-responsiveness [6]. In spondyloarthritis pre-clinical models, genetic deletion or blockade of MIF reduced the severity of inflammation [5].

In conclusion, MIF is a multifaceted cytokine involved in numerous biological processes and diseases. Model-based research, especially using MIF knockout or conditional knockout mouse models, has revealed its crucial roles in inflammation, cell death, and immune-related diseases such as ischemic brain injury, allergic asthma, and spondyloarthritis. These studies provide insights into potential therapeutic strategies targeting MIF for treating related diseases.