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rdf:type |
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lifeskim:mentions |
umls-concept:C0017262,
umls-concept:C0017337,
umls-concept:C0024320,
umls-concept:C0040113,
umls-concept:C0079189,
umls-concept:C0185117,
umls-concept:C0205250,
umls-concept:C0332282,
umls-concept:C0333641,
umls-concept:C0812246,
umls-concept:C1456820,
umls-concept:C1708726,
umls-concept:C2700640,
umls-concept:C2911684
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pubmed:issue |
10
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pubmed:dateCreated |
2009-10-7
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pubmed:abstractText |
TNF, lymphotoxin (LT)-alpha, LT-beta and LIGHT are members of a larger superfamily of TNF-related cytokines that can cross-utilize several receptors. Although LIGHT has been implicated in thymic development and function, the role of TNF and LT remains incompletely defined. To address this, we created a model of modest homeostatic overexpression of TNF/LT cytokines using the genomic human TNF/LT locus as a low copy number Tg. Strikingly, expression of Tg TNF/LT gene products led to profound early thymic atrophy characterized by decreased numbers of thymocytes and cortical thymic epithelial cells, partial block of thymocyte proliferation at double negative (DN) 1 stage, increased apoptosis of DN2 thymocytes and severe decline of T-cell numbers in the periphery. Results of backcrossing to TNFR1-, LTbetaR- or TNF/LT-deficient backgrounds and of reciprocal bone marrow transfers implicated both LT-alpha/LT-beta to LTbetaR and TNF/LT-alpha to TNFR1 signaling in accelerated thymus degeneration. We hypothesize that chronic infections can promote thymic atrophy by upregulating LT and TNF production.
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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/Keratin-8,
http://linkedlifedata.com/resource/pubmed/chemical/Krt8 protein, mouse,
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/Lymphotoxin-beta,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor...,
http://linkedlifedata.com/resource/pubmed/chemical/Tnfrsf1a protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1521-4141
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pubmed:author |
pubmed-author:DrutskayaMarina SMS,
pubmed-author:FeigenbaumLionelL,
pubmed-author:GalimovArthur RAR,
pubmed-author:GrivennikovSergei ISI,
pubmed-author:KruglovAndrei AAA,
pubmed-author:KuchmiyAnna AAA,
pubmed-author:KuprashDmitry VDV,
pubmed-author:LiepinshDmitry JDJ,
pubmed-author:NedospasovSergei ASA,
pubmed-author:ShakhovAlexander NAN,
pubmed-author:ShebzukhovYuriy VYV,
pubmed-author:TumanovAlexei VAV
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pubmed:issnType |
Electronic
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pubmed:volume |
39
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2906-15
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pubmed:dateRevised |
2011-5-5
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pubmed:meshHeading |
pubmed-meshheading:19735075-Animals,
pubmed-meshheading:19735075-Apoptosis,
pubmed-meshheading:19735075-Atrophy,
pubmed-meshheading:19735075-Bone Marrow Transplantation,
pubmed-meshheading:19735075-Cell Count,
pubmed-meshheading:19735075-Cell Proliferation,
pubmed-meshheading:19735075-Epithelial Cells,
pubmed-meshheading:19735075-Gene Dosage,
pubmed-meshheading:19735075-Gene Expression,
pubmed-meshheading:19735075-Humans,
pubmed-meshheading:19735075-Keratin-8,
pubmed-meshheading:19735075-Lymphotoxin beta Receptor,
pubmed-meshheading:19735075-Lymphotoxin-alpha,
pubmed-meshheading:19735075-Lymphotoxin-beta,
pubmed-meshheading:19735075-Mice,
pubmed-meshheading:19735075-Mice, Inbred C57BL,
pubmed-meshheading:19735075-Mice, Knockout,
pubmed-meshheading:19735075-Mice, Transgenic,
pubmed-meshheading:19735075-Receptors, Tumor Necrosis Factor, Type I,
pubmed-meshheading:19735075-Stem Cells,
pubmed-meshheading:19735075-T-Lymphocyte Subsets,
pubmed-meshheading:19735075-T-Lymphocytes,
pubmed-meshheading:19735075-Thymus Gland,
pubmed-meshheading:19735075-Tumor Necrosis Factor-alpha
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pubmed:year |
2009
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pubmed:articleTitle |
Accelerated thymic atrophy as a result of elevated homeostatic expression of the genes encoded by the TNF/lymphotoxin cytokine locus.
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pubmed:affiliation |
Laboratory of Molecular Immunology, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991, Moscow, Russia.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural,
Research Support, N.I.H., Intramural
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