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http://hdl.handle.net/1942/21356
Title: | Macrophages as mediators of protective autoimmunity in multiple sclerosis | Authors: | BOGIE, Jeroen | Advisors: | HENDRIKS, Jerome HELLINGS, Niels STINISSEN, Piet |
Issue Date: | 2013 | Abstract: | MS is a chronic, inflammatory, neurodegenerative disorder, in which macrophage-mediated myelin destruction is considered to be one the primary effector mechanism. Nonetheless, especially after internalization of myelin, macrophages have been described to obtain a less inflammatory phenotype. However, it is unclear by which mechanisms myelin affects the phenotype of macrophages and how this phenotype can influence lesion progression. ... The relapsing-remitting nature of MS suggests the presence of naturallyoccurring regulatory mechanisms in the disease, which may be harnessed for future intervention strategies aimed at reducing neuroinflammation and stimulation CNS repair. In this thesis we show that myelin internalization by macrophages induces a less inflammatory, immunesuppressive phenotype in macrophages, indicating that myelin-phagocytosing macrophages may contribute to the remission phase observed in relapse-remitting MS patients. By affecting autoreactive T cell function, either in lymphoid organs or locally in the CNS, they can dampen the inflammatory burden in MS-affected individuals. Moreover, the suppressed production of inflammatory mediators by myelinphagocytosing macrophages can repress demyelination and axonal degeneration, and may create an environment more susceptible for repair. To date, despite the abundance of lipids in myelin, most studies have mainly focused on the role of myelin proteins in demyelinating diseases. Our data indicate a role for myelin-derived lipids in modulating the metabolic and inflammatory response in macrophages during demyelination. By modulating the macrophage phenotype through activation of LXRβ and PPARβ/δ, myelin-derived lipids may affect lesion progression in MS. This unrecognized link between demyelination, lipid metabolism and macrophage-mediated inflammation during MS pathogenesis holds promise for future MS therapeutics. | Document URI: | http://hdl.handle.net/1942/21356 | Category: | T1 | Type: | Theses and Dissertations |
Appears in Collections: | PhD theses Research publications |
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Doctoraat_Jeroen Bogie.pdf | 3.77 MB | Adobe PDF | View/Open |
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