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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
Pt 2
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pubmed:dateCreated |
2010-2-17
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pubmed:abstractText |
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.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145049-10499442,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145049-10759704,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145049-10800162,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145049-11135576,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145049-11161453,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145049-11739179,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145049-12422218,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145049-12471103,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145049-1373228,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145049-1423621,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145049-14622116,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145049-14987990,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145049-15100285,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145049-15539157,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145049-16284246,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145049-16343423,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145049-16543951,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145049-18815152,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145049-18973947,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145049-19143847,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145049-19204074,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145049-1969332,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145049-2466079,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145049-2545785,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145049-6193236,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145049-7520367,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145049-7679952,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145049-7999308,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145049-8635458,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145049-9794251
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1460-2156
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pubmed:author |
pubmed-author:BenLi-HongLH,
pubmed-author:BreilAndreasA,
pubmed-author:ChiangY CYC,
pubmed-author:CravensPetra DPD,
pubmed-author:EagarTodd NTN,
pubmed-author:ElliottJeffrey LJL,
pubmed-author:GockeAnne RAR,
pubmed-author:HemmerBernhardB,
pubmed-author:HussainRehana ZRZ,
pubmed-author:KaneLawrence PLP,
pubmed-author:KorthCarstenC,
pubmed-author:LeliveldS RutgerSR,
pubmed-author:Lovett-RackeAmyA,
pubmed-author:NesslerStefanS,
pubmed-author:PetschBenjaminB,
pubmed-author:PuttaparthiKrishnaK,
pubmed-author:RackeMichael KMK,
pubmed-author:SinghMahendra PMP,
pubmed-author:StüveOlafO,
pubmed-author:StitzLotharL,
pubmed-author:YaoQQ
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pubmed:issnType |
Electronic
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pubmed:volume |
133
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
375-88
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pubmed:dateRevised |
2010-9-27
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pubmed:meshHeading |
pubmed-meshheading:20145049-Animals,
pubmed-meshheading:20145049-Demyelinating Autoimmune Diseases, CNS,
pubmed-meshheading:20145049-Female,
pubmed-meshheading:20145049-Gene Silencing,
pubmed-meshheading:20145049-Mice,
pubmed-meshheading:20145049-Mice, Inbred C57BL,
pubmed-meshheading:20145049-Mice, Transgenic,
pubmed-meshheading:20145049-Prions,
pubmed-meshheading:20145049-RNA, Small Interfering,
pubmed-meshheading:20145049-Receptors, Antigen, T-Cell,
pubmed-meshheading:20145049-Signal Transduction
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pubmed:year |
2010
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pubmed:articleTitle |
Pharmacological prion protein silencing accelerates central nervous system autoimmune disease via T cell receptor signalling.
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pubmed:affiliation |
Department of Neurology, University of Texas Southwestern Medical Center at Dallas, TX, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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