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- Joanna Mikita, Nadège Dubourdieu-Cassagno, Mathilde Sa Deloire, Antoine Vekris, Marc Biran, Gérard Raffard, Bruno Brochet, Marie-Hélène Canron, Jean-Michel Franconi, Claudine Boiziau, and Klaus G Petry.
- University Victor Segalen, France.
- Mult. Scler. 2011 Jan 1; 17 (1): 2-15.
ObjectivesWe investigated proinflammatory M1 and immunomodulatory M2 activation profiles of circulating monocytes in relapsing experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis, and tested whether altered M1/M2 equilibrium promotes CNS inflammation.ResultsApproaches of MRI macrophage tracking with USPIO nanoparticles and expression patterns of M1/M2 macrophages and microglia in brain and M1/M2 monocytes in blood samples at various disease stages revealed that M1/M2 equilibrium in blood and CNS favors mild EAE, while imbalance towards M1 promotes relapsing EAE. We consequently investigated whether M2 activated monocyte restoration in peripheral blood could cure acute clinical EAE disease. Administration of ex vivo activated M2 monocytes both suppressed ongoing severe EAE and increased immunomodulatory expression pattern in lesions, confirming their role in the induction of recovery.ConclusionWe conclude that imbalance of monocyte activation profiles and impaired M2 expression, are key factors in development of relapses. Our study opens new perspectives for therapeutic applications in MS.
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