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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7
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pubmed:dateCreated |
2009-4-2
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pubmed:abstractText |
The Ca(2+)-regulated calcineurin/nuclear factor of activated T cells (NFAT) cascade controls alternative pathways of T-cell activation and peripheral tolerance. Here, we describe reduction of NFATc2 mRNA expression in the lungs of patients with bronchial adenocarcinoma. In a murine model of bronchoalveolar adenocarcinoma, mice lacking NFATc2 developed more and larger solid tumors than wild-type littermates. The extent of central tumor necrosis was decreased in the tumors in NFATc2((-/-)) mice, and this finding was associated with reduced tumor necrosis factor-alpha and interleukin-2 (IL-2) production by CD8(+) T cells. Adoptive transfer of CD8(+) T cells of NFATc2((-/-)) mice induced transforming growth factor-beta(1) in the airways of recipient mice, thus supporting CD4(+)CD25(+)Foxp-3(+)glucocorticoid-induced tumor necrosis factor receptor (GITR)(+) regulatory T (T(reg)) cell survival. Finally, engagement of GITR in NFATc2((-/-)) mice induced IFN-gamma levels in the airways, reversed the suppression by T(reg) cells, and costimulated effector CD4(+)CD25(+) (IL-2Ralpha) and memory CD4(+)CD127(+) (IL-7Ralpha) T cells, resulting in abrogation of carcinoma progression. Agonistic signaling through GITR, in the absence of NFATc2, thus emerges as a novel possible strategy for the treatment of human bronchial adenocarcinoma in the absence of NFATc2 by enhancing IL-2Ralpha(+) effector and IL-7Ralpha(+) memory-expressing T cells.
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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/Forkhead Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Foxp3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Glucocorticoid-Induced...,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-2 Receptor alpha Subunit,
http://linkedlifedata.com/resource/pubmed/chemical/NFATC Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/NFATC2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-7,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Nerve Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Tnfrsf18 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta1,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/interleukin-7 receptor, alpha chain
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1538-7445
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pubmed:author |
pubmed-author:BorossIldikoI,
pubmed-author:FinottoSusettaS,
pubmed-author:KarwotRomanR,
pubmed-author:KoslowskiMichaelM,
pubmed-author:LehrHans AHA,
pubmed-author:MaxeinerJoachim HJH,
pubmed-author:NeurathMarkus FMF,
pubmed-author:SauerKerstinK,
pubmed-author:ScholtesPetraP,
pubmed-author:TüreciOzlemO,
pubmed-author:WiewrodtRainerR
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
69
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3069-76
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:19318584-Adenocarcinoma,
pubmed-meshheading:19318584-Animals,
pubmed-meshheading:19318584-Bronchial Neoplasms,
pubmed-meshheading:19318584-CD4-Positive T-Lymphocytes,
pubmed-meshheading:19318584-CD8-Positive T-Lymphocytes,
pubmed-meshheading:19318584-Disease Models, Animal,
pubmed-meshheading:19318584-Forkhead Transcription Factors,
pubmed-meshheading:19318584-Glucocorticoid-Induced TNFR-Related Protein,
pubmed-meshheading:19318584-Humans,
pubmed-meshheading:19318584-Interferon-gamma,
pubmed-meshheading:19318584-Interleukin-2,
pubmed-meshheading:19318584-Interleukin-2 Receptor alpha Subunit,
pubmed-meshheading:19318584-Mice,
pubmed-meshheading:19318584-Mice, Inbred BALB C,
pubmed-meshheading:19318584-Mice, Transgenic,
pubmed-meshheading:19318584-NFATC Transcription Factors,
pubmed-meshheading:19318584-Receptors, Interleukin-7,
pubmed-meshheading:19318584-Receptors, Nerve Growth Factor,
pubmed-meshheading:19318584-Receptors, Tumor Necrosis Factor,
pubmed-meshheading:19318584-Transcription, Genetic,
pubmed-meshheading:19318584-Transforming Growth Factor beta1,
pubmed-meshheading:19318584-Transplantation, Heterologous,
pubmed-meshheading:19318584-Tumor Necrosis Factor-alpha
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pubmed:year |
2009
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pubmed:articleTitle |
A key regulatory role of the transcription factor NFATc2 in bronchial adenocarcinoma via CD8+ T lymphocytes.
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pubmed:affiliation |
Laboratory of Cellular and Molecular Immunology of the Lung, I. Medical Clinic, University of Mainz, Mainz, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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