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http://purl.uniprot.org/citations/20145049http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/20145049http://www.w3.org/2000/01/rdf-schema#comment"The primary biological function of the endogenous cellular prion protein has remained unclear. We investigated its biological function in the generation of cellular immune responses using cellular prion protein gene-specific small interfering ribonucleic acid in vivo and in vitro. Our results were confirmed by blocking cellular prion protein with monovalent antibodies and by using cellular prion protein-deficient and -transgenic mice. In vivo prion protein gene-small interfering ribonucleic acid treatment effects were of limited duration, restricted to secondary lymphoid organs and resulted in a 70% reduction of cellular prion protein expression in leukocytes. Disruption of cellular prion protein signalling augmented antigen-specific activation and proliferation, and enhanced T cell receptor signalling, resulting in zeta-chain-associated protein-70 phosphorylation and nuclear factor of activated T cells/activator protein 1 transcriptional activity. In vivo prion protein gene-small interfering ribonucleic acid treatment promoted T cell differentiation towards pro-inflammatory phenotypes and increased survival of antigen-specific T cells. Cellular prion protein silencing with small interfering ribonucleic acid also resulted in the worsening of actively induced and adoptively transferred experimental autoimmune encephalomyelitis. Finally, treatment of myelin basic protein(1-11) T cell receptor transgenic mice with prion protein gene-small interfering ribonucleic acid resulted in spontaneous experimental autoimmune encephalomyelitis. Thus, central nervous system autoimmune disease was modulated at all stages of disease: the generation of the T cell effector response, the elicitation of T effector function and the perpetuation of cellular immune responses. Our findings indicate that cellular prion protein regulates T cell receptor-mediated T cell activation, differentiation and survival. Defects in autoimmunity are restricted to the immune system and not the central nervous system. Our data identify cellular prion protein as a regulator of cellular immunological homoeostasis and suggest cellular prion protein as a novel potential target for therapeutic immunomodulation."xsd:string
http://purl.uniprot.org/citations/20145049http://purl.org/dc/terms/identifier"doi:10.1093/brain/awp298"xsd:string
http://purl.uniprot.org/citations/20145049http://purl.uniprot.org/core/author"Hu W."xsd:string
http://purl.uniprot.org/citations/20145049http://purl.uniprot.org/core/author"Nessler S."xsd:string
http://purl.uniprot.org/citations/20145049http://purl.uniprot.org/core/author"Elliott J.L."xsd:string
http://purl.uniprot.org/citations/20145049http://purl.uniprot.org/core/author"Stitz L."xsd:string
http://purl.uniprot.org/citations/20145049http://purl.uniprot.org/core/author"Kane L.P."xsd:string
http://purl.uniprot.org/citations/20145049http://purl.uniprot.org/core/author"Singh M.P."xsd:string
http://purl.uniprot.org/citations/20145049http://purl.uniprot.org/core/author"Hemmer B."xsd:string
http://purl.uniprot.org/citations/20145049http://purl.uniprot.org/core/author"Racke M.K."xsd:string
http://purl.uniprot.org/citations/20145049http://purl.uniprot.org/core/author"Korth C."xsd:string
http://purl.uniprot.org/citations/20145049http://purl.uniprot.org/core/author"Puttaparthi K."xsd:string
http://purl.uniprot.org/citations/20145049http://purl.uniprot.org/core/author"Stuve O."xsd:string
http://purl.uniprot.org/citations/20145049http://purl.uniprot.org/core/author"Hussain R.Z."xsd:string
http://purl.uniprot.org/citations/20145049http://purl.uniprot.org/core/author"Eagar T.N."xsd:string
http://purl.uniprot.org/citations/20145049http://purl.uniprot.org/core/author"Leliveld S.R."xsd:string
http://purl.uniprot.org/citations/20145049http://purl.uniprot.org/core/author"Ben L.H."xsd:string
http://purl.uniprot.org/citations/20145049http://purl.uniprot.org/core/author"Cravens P.D."xsd:string
http://purl.uniprot.org/citations/20145049http://purl.uniprot.org/core/author"Gocke A.R."xsd:string
http://purl.uniprot.org/citations/20145049http://purl.uniprot.org/core/author"Muller-Schiffmann A."xsd:string
http://purl.uniprot.org/citations/20145049http://purl.uniprot.org/core/author"Breil A."xsd:string
http://purl.uniprot.org/citations/20145049http://purl.uniprot.org/core/author"Lovett-Racke A."xsd:string
http://purl.uniprot.org/citations/20145049http://purl.uniprot.org/core/author"Petsch B."xsd:string
http://purl.uniprot.org/citations/20145049http://purl.uniprot.org/core/date"2010"xsd:gYear
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