title: Absence of the cellular prion protein exacerbates and prolongs neuroinflammation in experimental autoimmune encephalomyelitis.
abstract: Although the physiological roles of the cellular prion protein (PrP C) remain to be fully elucidated, PrP C has been proposed to represent a potential regulator of cellular immunity. To test this hypothesis, we evaluated the consequences of PrP C deficiency on the course of experimental autoimmune encephalomyelitis induced by immunization with myelin oligodendrocyte glycoprotein peptide. Consistent with augmented proliferative responses and increased cytokine gene expression by myelin oligodendrocyte glycoprotein-primed Prnp-/- T cells, PrP C-deficient mice demonstrated more aggressive disease onset and a lack of clinical improvement during the chronic phase of experimental autoimmune encephalomyelitis. Acutely, Prnp-/- spinal cord, cerebellum, and forebrain exhibited higher levels of leukocytic infiltrates and pro-inflammatory cytokine gene expression, as well as increased spinal cord myelin basic protein and axonal loss. During the chronic phase, a remarkable persistence of leukocytic infiltrates was present in the forebrain and cerebellum, accompanied by an increase in interferon-gamma and interleukin-17 transcripts. Attenuation of T cell-dependent neuroinflammation thus represents a potential novel function of PrP C.
authors.affiliation: Department of Biochemistry and Molecular Biology, McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Tsutsui
authors.forename: Jennifer N
authors.initials: JN
authors.lastname: Hahn
authors.forename: Trina A
authors.initials: TA
authors.lastname: Johnson
authors.forename: Zenobia
authors.initials: Z
authors.lastname: Ali
authors.forename: Frank R
authors.initials: FR
authors.lastname: Jirik
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002531:Cerebellum / Q000473:pathology; D045142:Cross-Priming; D003713:Dendritic Cells / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism / Q000473:pathology*; D007114:Immunization; D007249:Inflammation; D018836:Inflammation Mediators / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D009420:Nervous System / Q000378:metabolism / Q000473:pathology*; D018621:PrPC Proteins / Q000172:deficiency* / Q000378:metabolism; D016548:Prosencephalon / Q000473:pathology; D013116:Spinal Cord / Q000473:pathology; D015854:Up-Regulation
chemical_list: D018836:Inflammation Mediators; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D018621:PrPC Proteins