Project R-6425

Fatty acid metabolism in control of the phenotype of phagocytes in MS lesions (Research)

Multiple sclerosis (MS) is a neurodegenerative autoimmune disease of the central nervous system (CNS) in which macrophages and microglia play a crucial role. Driving these phagocytes towards an anti-inflammatory and regenerative phenotype is considered a promising strategy to halt MS disease progression. Of particular interest are approaches that exploit naturally occurring pathways that induce this phenotype in phagocytes. Myelin-containing phagocytes are the most abundant cell type in MS lesions and display immunosuppressive and neuroprotective features. However, to date, the hubs and drivers of this phenotype, as well as the effect that these phagocytes have on MS lesion progression, remain poorly understood. My preliminary data suggest that fatty acid metabolism is key in driving the characteristic phenotype of macrophages upon myelin uptake. By using a combination of primary mouse/human phagocyte cultures and animal models, I here define how fatty acid metabolism impacts the phenotype of phagocytes after myelin uptake, as well as its impact on neuroinflammation and CNS repair. By doing so, obtained results will lead to increased insights into CNS lesion development and repair, and to the development of promising new strategies in the treatment of CNS disorders.

01 October 2015 - 30 September 2018