| pubmed-article:20145049 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:20145049 | lifeskim:mentions | umls-concept:C0033164 | lld:lifeskim |
| pubmed-article:20145049 | lifeskim:mentions | umls-concept:C0004364 | lld:lifeskim |
| pubmed-article:20145049 | lifeskim:mentions | umls-concept:C0927232 | lld:lifeskim |
| pubmed-article:20145049 | lifeskim:mentions | umls-concept:C0034790 | lld:lifeskim |
| pubmed-article:20145049 | lifeskim:mentions | umls-concept:C1710082 | lld:lifeskim |
| pubmed-article:20145049 | lifeskim:mentions | umls-concept:C0205464 | lld:lifeskim |
| pubmed-article:20145049 | pubmed:issue | Pt 2 | lld:pubmed |
| pubmed-article:20145049 | pubmed:dateCreated | 2010-2-17 | lld:pubmed |
| pubmed-article:20145049 | 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. | lld:pubmed |
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| pubmed-article:20145049 | pubmed:language | eng | lld:pubmed |
| pubmed-article:20145049 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20145049 | pubmed:citationSubset | AIM | lld:pubmed |
| pubmed-article:20145049 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:20145049 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20145049 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:20145049 | pubmed:month | Feb | lld:pubmed |
| pubmed-article:20145049 | pubmed:issn | 1460-2156 | lld:pubmed |
| pubmed-article:20145049 | pubmed:author | pubmed-author:ChiangY CYC | lld:pubmed |
| pubmed-article:20145049 | pubmed:author | pubmed-author:YaoQQ | lld:pubmed |
| pubmed-article:20145049 | pubmed:author | pubmed-author:StitzLotharL | lld:pubmed |
| pubmed-article:20145049 | pubmed:author | pubmed-author:HussainRehana... | lld:pubmed |
| pubmed-article:20145049 | pubmed:author | pubmed-author:RackeMichael... | lld:pubmed |
| pubmed-article:20145049 | pubmed:author | pubmed-author:HemmerBernhar... | lld:pubmed |
| pubmed-article:20145049 | pubmed:author | pubmed-author:EagarTodd NTN | lld:pubmed |
| pubmed-article:20145049 | pubmed:author | pubmed-author:NesslerStefan... | lld:pubmed |
| pubmed-article:20145049 | pubmed:author | pubmed-author:KaneLawrence... | lld:pubmed |
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| pubmed-article:20145049 | pubmed:author | pubmed-author:ElliottJeffre... | lld:pubmed |
| pubmed-article:20145049 | pubmed:author | pubmed-author:BenLi-HongLH | lld:pubmed |
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| pubmed-article:20145049 | pubmed:author | pubmed-author:KorthCarstenC | lld:pubmed |
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| pubmed-article:20145049 | pubmed:author | pubmed-author:GockeAnne RAR | lld:pubmed |
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| pubmed-article:20145049 | pubmed:author | pubmed-author:BreilAndreasA | lld:pubmed |
| pubmed-article:20145049 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:20145049 | pubmed:volume | 133 | lld:pubmed |
| pubmed-article:20145049 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:20145049 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:20145049 | pubmed:pagination | 375-88 | lld:pubmed |
| pubmed-article:20145049 | pubmed:dateRevised | 2010-9-27 | lld:pubmed |
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| pubmed-article:20145049 | pubmed:year | 2010 | lld:pubmed |
| pubmed-article:20145049 | pubmed:articleTitle | Pharmacological prion protein silencing accelerates central nervous system autoimmune disease via T cell receptor signalling. | lld:pubmed |
| pubmed-article:20145049 | pubmed:affiliation | Department of Neurology, University of Texas Southwestern Medical Center at Dallas, TX, USA. | lld:pubmed |
| pubmed-article:20145049 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:20145049 | pubmed:publicationType | Comparative Study | lld:pubmed |
| pubmed-article:20145049 | pubmed:publicationType | Research Support, U.S. Gov't, Non-P.H.S. | lld:pubmed |
| pubmed-article:20145049 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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