Skip to main content
Fig. 3 | Acta Neuropathologica Communications

Fig. 3

From: The physiology of foamy phagocytes in multiple sclerosis

Fig. 3

Foamy phagocyte polarization follows a triphasic pattern. Uptake of myelin initially promotes the induction of a disease-promoting phenotype of phagocytes, characterized by an increased release of inflammatory and toxic mediators, and reduced production of anti-inflammatory factors (phase I). The induction of this phenotype likely relies on the rapid activation of the FAK/PI3K/Akt/NF-κB signaling pathway following ligation of the complement receptor 3 (CR3). In time, intracellular processing of myelin will generate lipid metabolites capable of activating the anti-inflammatory liver X receptor (LXR) and peroxisome proliferator-activated receptor (PPAR). Activation of these nuclear receptors will repress the inflammatory transcriptional profile in macrophages (phase II). With aging, an inability of phagocytes to process and efflux the enormous amounts of intracellular cholesterol-rich myelin debris results in the formation of cholesterol crystals that activate the NLRP3 inflammasome (phase III)

Back to article page
\