Vitamin D₃ and Monomethyl Fumarate Enhance Natural Killer Cell Lysis of Dendritic Cells and Ameliorate the Clinical Score in Mice Suffering from Experimental Autoimmune Encephalomyelitis

摘要

Experimental autoimmune encephalomyelitis (EAE) is a CD4+ T cell mediated inflammatory demyelinating disease that is induced in mice by administration of peptides derived from myelin proteins. We developed EAE in SJL mice by administration of PLP_139–151 peptide. The effect of treating these mice with 1α,25-Dihydroxyvitamin D₃ (vitamin D₃), or with monomethyl fumarate (MMF) was then examined. We observed that both vitamin D₃ and MMF inhibited and/or prevented EAE in these mice. These findings were corroborated with isolating natural killer (NK) cells from vitamin D₃-treated or MMF-treated EAE mice that lysed immature or mature dendritic cells. The results support and extend other findings indicating that an important mechanism of action for drugs used to treat multiple sclerosis (MS) is to enhance NK cell lysis of dendritic cells.