title: Apolipoprotein E mediation of neuro-inflammation in a murine model of multiple sclerosis.
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.
authors.affiliation: Department of Neurology, Washington University in St. Louis School of Medicine, Box 8111, 660 S. Euclid Avenue, St. Louis, MO 63110, United States.
authors.forename: Soomin
authors.initials: S
authors.lastname: Shin
authors.affiliation: Department of Neurology, Washington University in St. Louis School of Medicine, Box 8111, 660 S. Euclid Avenue, St. Louis, MO 63110, United States.
authors.forename: Katharine A
authors.initials: KA
authors.lastname: Walz
authors.affiliation: Department of Neurology, Washington University in St. Louis School of Medicine, Box 8111, 660 S. Euclid Avenue, St. Louis, MO 63110, United States.
authors.forename: Angela S
authors.initials: AS
authors.lastname: Archambault
authors.affiliation: Department of Developmental Biology, Washington University in St. Louis School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, United States.
authors.forename: Julia
authors.initials: J
authors.lastname: Sim
authors.affiliation: Department of Neurology, Washington University in St. Louis School of Medicine, Box 8111, 660 S. Euclid Avenue, St. Louis, MO 63110, United States.
authors.forename: Bryan P
authors.initials: BP
authors.lastname: Bollman
authors.affiliation: Department of Neurology, Washington University in St. Louis School of Medicine, Box 8111, 660 S. Euclid Avenue, St. Louis, MO 63110, United States.
authors.forename: Jessica
authors.initials: J
authors.lastname: Koenigsknecht-Talboo
authors.affiliation: Department of Neurology, Washington University in St. Louis School of Medicine, Box 8111, 660 S. Euclid Avenue, St. Louis, MO 63110, United States; Hope Center for Neurological Disorders, Washington University in St. Louis School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, United States.
authors.forename: Anne H
authors.initials: AH
authors.lastname: Cross
authors.affiliation: Department of Neurology, Washington University in St. Louis School of Medicine, Box 8111, 660 S. Euclid Avenue, St. Louis, MO 63110, United States; Department of Developmental Biology, Washington University in St. Louis School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, United States; Hope Center for Neurological Disorders, Washington University in St. Louis School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, United States.
authors.forename: David M
authors.initials: DM
authors.lastname: Holtzman
authors.affiliation: Department of Neurology, Washington University in St. Louis School of Medicine, Box 8111, 660 S. Euclid Avenue, St. Louis, MO 63110, United States; Hope Center for Neurological Disorders, Washington University in St. Louis School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, United States; Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, United States. Electronic address: wug@neuro.wustl.edu.
authors.forename: Gregory F
authors.initials: GF
authors.lastname: Wu
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D000073883:CX3C Chemokine Receptor 1; D002490:Central Nervous System / Q000473:pathology*; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D004660:Encephalitis / Q000139:chemically induced / Q000209:etiology / Q000235:genetics / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000150:complications* / Q000235:genetics; D005620:Freund's Adjuvant; D007963:Leukocytes, Mononuclear / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009103:Multiple Sclerosis / Q000150:complications* / Q000235:genetics; D019707:Receptors, Chemokine / Q000235:genetics; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology
chemical_list: D001057:Apolipoproteins E; D000073883:CX3C Chemokine Receptor 1; C471885:Cx3cr1 protein, mouse; D019707:Receptors, Chemokine; D005620:Freund's Adjuvant
keywords: Antigen presentation; Apolipoprotein E; Dendritic cells; EAE