“Lipid metabolism is key in driving the detrimental properties of macrophages in multiple sclerosis lesions”

(MS) lesions are characterized by excessive infiltration of immune cells, such as macrophages. To date, it remains unclear how these cells impact the initiation and progression of MS lesions. While some studies indicate that they are the “bad” guys, other studies defined protective features of macrophages. Our recent findings indicate that lipids are key in driving the detrimental properties of macrophages in MS lesions. In this study, we unravel whether MS patients at different disease stages show changes in lipids of interest. Eventually, our findings can explain disease progression and ultimately lead to new and improved therapies.

The scientific project

Multiple sclerosis (MS) is a neurodegenerative autoimmune disease of the central nervous system in which phagocytes play a crucial role. Myelin-containing phagocytes are the most abundant cell type in MS lesions and display a transient wound-healing phenotype. To date, the hubs and drivers of this phenotype remain poorly understood. Our recent data indicate that prolonged intracellular myelin accumulation disturbs the wound-healing phenotype of myelin-containing phagocytes. Furthermore, our data show that an enzyme involved in fatty acid metabolism underlies this inflammatory phenotype shift. Importantly, animals lacking this enzyme demonstrate reduced neuroinflammation and enhanced CNS repair in in vivo models. In this study, we validate and elaborate on the role of this enzyme in driving the phenotype of phagocytes in MS patients.