Source:http://linkedlifedata.com/resource/pubmed/id/20974984
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
11
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| pubmed:dateCreated |
2010-11-18
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| pubmed:abstractText |
Given the association with autoimmune disease, there is great interest in defining cellular factors that limit overactive or misdirected Th17-type inflammation. Using in vivo and in vitro models, we investigated the molecular mechanisms for cytokine-mediated inhibition of Th17 responses, focusing on the role of STAT1 and T-bet in this process. These studies demonstrate that, during systemic inflammation, STAT1- and T-bet-deficient T cells each exhibit a hyper-Th17 phenotype relative to wild-type controls. However, IL-17 production was greater in the absence of T-bet, and when both STAT1 and T-bet were deleted, there was no further increase, with the double-deficient cells instead behaving more like STAT1-deficient counterparts. Similar trends were observed during in vitro priming, with production of Th17-type cytokines greater in T-bet(-/-) T cells than in either STAT1(-/-) or STAT1(-/-) T-bet(-/-) counterparts. The ability of IFN-? and IL-27 to suppress Th17 responses was reduced in T-bet-deficient cells, and most importantly, ectopic T-bet could suppress signature Th17 gene products, including IL-17A, IL-17F, IL-22, and retinoic acid-related orphan receptor ?T, even in STAT1-deficient T cells. Taken together, these studies formally establish that, downstream of IFN-?, IL-27, and likely all STAT1-activating cytokines, there are both STAT1 and T-bet-dependent pathways capable of suppressing Th17 responses.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/Il27 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Inflammation Mediators,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-17,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukins,
http://linkedlifedata.com/resource/pubmed/chemical/STAT1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Stat1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/T-Box Domain Proteins
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| pubmed:status |
MEDLINE
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| pubmed:month |
Dec
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| pubmed:issn |
1550-6606
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:day |
1
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| pubmed:volume |
185
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
6461-71
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| pubmed:meshHeading |
pubmed-meshheading:20974984-Animals,
pubmed-meshheading:20974984-Autoimmune Diseases,
pubmed-meshheading:20974984-Cells, Cultured,
pubmed-meshheading:20974984-Cytokines,
pubmed-meshheading:20974984-Immunophenotyping,
pubmed-meshheading:20974984-Inflammation Mediators,
pubmed-meshheading:20974984-Interferon-gamma,
pubmed-meshheading:20974984-Interleukin-17,
pubmed-meshheading:20974984-Interleukins,
pubmed-meshheading:20974984-Lymphopenia,
pubmed-meshheading:20974984-Mice,
pubmed-meshheading:20974984-Mice, Inbred BALB C,
pubmed-meshheading:20974984-Mice, Knockout,
pubmed-meshheading:20974984-Mice, Transgenic,
pubmed-meshheading:20974984-STAT1 Transcription Factor,
pubmed-meshheading:20974984-Signal Transduction,
pubmed-meshheading:20974984-T-Box Domain Proteins,
pubmed-meshheading:20974984-T-Lymphocyte Subsets,
pubmed-meshheading:20974984-Th1 Cells
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| pubmed:year |
2010
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| pubmed:articleTitle |
STAT1-activating cytokines limit Th17 responses through both T-bet-dependent and -independent mechanisms.
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| pubmed:affiliation |
Department of Pathology, University of California San Francisco, San Francisco, CA 94143, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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