Absence of the cellular prion protein exacerbates and prolongs neuroinflammation in experimental autoimmune encephalomyelitis.
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.
Tsutsui
Shigeki
S
Department of Biochemistry and Molecular Biology, McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, Alberta, Canada.
Hahn
Jennifer N
JN
Johnson
Trina A
TA
Ali
Zenobia
Z
Jirik
Frank R
FR
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
D018836:Inflammation Mediators; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D018621:PrPC Proteins