Abstract
Apolipoprotein E (ApoE) functions as a ligand in receptor-mediated endocytosis of lipoprotein particles and has been demonstrated to play a role in antigen presentation. To explore the contribution of ApoE during autoimmune central nervous system (CNS) demyelination, we examined the clinical, cellular immune function, and pathologic consequences of experimental autoimmune encephalomyelitis (EAE) induction in ApoE knockout (ApoE(-/-)) mice. We observed reduced clinical severity of EAE in ApoE(-/-) mice in comparison to WT mice that was concomitant with an early reduction of dendritic cells (DCs) followed by a reduction of additional innate cells in the spinal cord at the peak of disease without any differences in axonal damage. While T cell priming was enhanced in ApoE(-/-) mice, reduced severity of EAE was also observed in ApoE(-/-) recipients of encephalitogenic wild type T cells. Expression of ApoE during EAE was elevated within the CNS of wild type mice, particularly by innate cells such as DCs. Overall, ApoE promotes clinical EAE, likely by mediation of inflammation localized within the CNS.