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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2007-12-17
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pubmed:abstractText |
The activation of Toll-like receptors (TLRs) in dendritic cells (DCs) triggers a rapid inflammatory response to pathogens. However, this response must be tightly regulated because unrestrained TLR signaling generates a chronic inflammatory milieu that often leads to autoimmunity. We have found that the TAM receptor tyrosine kinases-Tyro3, Axl, and Mer-broadly inhibit both TLR and TLR-induced cytokine-receptor cascades. Remarkably, TAM inhibition of inflammation is transduced through an essential stimulator of inflammation-the type I interferon receptor (IFNAR)-and its associated transcription factor STAT1. TLR induction of IFNAR-STAT1 signaling upregulates the TAM system, which in turn usurps the IFNAR-STAT1 cassette to induce the cytokine and TLR suppressors SOCS1 and SOCS3. These results illuminate a self-regulating cycle of inflammation, in which the obligatory, cytokine-dependent activation of TAM signaling hijacks a proinflammatory pathway to provide an intrinsic feedback inhibitor of both TLR- and cytokine-driven immune responses.
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pubmed:grant |
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pubmed:commentsCorrections |
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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/Ifnar1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Mertk protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Interferon alpha-beta,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/STAT1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Socs1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Socs3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Stat1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Suppressor of Cytokine Signaling...,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptors,
http://linkedlifedata.com/resource/pubmed/chemical/Tyro3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/axl receptor tyrosine kinase
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0092-8674
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
14
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pubmed:volume |
131
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1124-36
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pubmed:dateRevised |
2010-6-2
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pubmed:meshHeading |
pubmed-meshheading:18083102-Animals,
pubmed-meshheading:18083102-Dendritic Cells,
pubmed-meshheading:18083102-Gene Expression Regulation,
pubmed-meshheading:18083102-Immunity, Innate,
pubmed-meshheading:18083102-Inflammation,
pubmed-meshheading:18083102-Mice,
pubmed-meshheading:18083102-Mice, Knockout,
pubmed-meshheading:18083102-Oncogene Proteins,
pubmed-meshheading:18083102-Proto-Oncogene Proteins,
pubmed-meshheading:18083102-Receptor, Interferon alpha-beta,
pubmed-meshheading:18083102-Receptor Protein-Tyrosine Kinases,
pubmed-meshheading:18083102-STAT1 Transcription Factor,
pubmed-meshheading:18083102-Signal Transduction,
pubmed-meshheading:18083102-Suppressor of Cytokine Signaling Proteins,
pubmed-meshheading:18083102-Toll-Like Receptors,
pubmed-meshheading:18083102-Ubiquitination
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pubmed:year |
2007
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pubmed:articleTitle |
TAM receptors are pleiotropic inhibitors of the innate immune response.
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pubmed:affiliation |
Molecular Neurobiology Laboratory, The Salk Institute, La Jolla, CA 92037, 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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