rdf:type |
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lifeskim:mentions |
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pubmed:issue |
11
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pubmed:dateCreated |
2003-10-30
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pubmed:abstractText |
The autoimmune regulator Aire is a key mediator of central tolerance for peripherally restricted antigens. Its absence in human patients results in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. The cellular signals that regulate Aire expression are undefined. We show here that lymphotoxin signaling is necessary for the expression of Aire and its downstream target genes. The failure of Aire induction in the thymi of lymphotoxin-deficient and lymphotoxin-beta receptor-deficient mice contributes to overt autoimmunity against self antigens normally protected by Aire. Conversely, stimulation of lymphotoxin-beta receptor by agonistic antibody leads to increased expression of Aire and tissue-restricted antigens in both intact thymi and cultured thymic epithelial cell line. These findings define the essential cross-talk between thymocytes and thymic stroma that is required for central tolerance.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/APECED protein,
http://linkedlifedata.com/resource/pubmed/chemical/Autoantibodies,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/LTBR protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Ltbr protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Lymphotoxin beta Receptor,
http://linkedlifedata.com/resource/pubmed/chemical/Lymphotoxin-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1529-2908
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pubmed:author |
|
pubmed:issnType |
Print
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pubmed:volume |
4
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1121-7
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:14517552-Animals,
pubmed-meshheading:14517552-Autoantibodies,
pubmed-meshheading:14517552-Immune Tolerance,
pubmed-meshheading:14517552-Insulin,
pubmed-meshheading:14517552-Lymphotoxin beta Receptor,
pubmed-meshheading:14517552-Lymphotoxin-alpha,
pubmed-meshheading:14517552-Mice,
pubmed-meshheading:14517552-Receptors, Tumor Necrosis Factor,
pubmed-meshheading:14517552-Signal Transduction,
pubmed-meshheading:14517552-Spleen,
pubmed-meshheading:14517552-Thymus Gland,
pubmed-meshheading:14517552-Transcription Factors
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pubmed:year |
2003
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pubmed:articleTitle |
Lymphotoxin pathway directs thymic Aire expression.
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pubmed:affiliation |
Department of Pathology and Committee in Immunology, The University of Chicago, Chicago, Illinois 60637, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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