Source:http://linkedlifedata.com/resource/pubmed/id/19620306
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
2009-8-7
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pubmed:abstractText |
The transcription factors mediating the development of CD1d-restricted invariant NKT (iNKT) cells remain incompletely described. Here, we show that loss of the AP-1 transcription factor Fra-2 causes a marked increase in the number of both thymic and peripheral iNKT cells, without affecting the development of other T-lineage cells. The defect is cell-autonomous and is evident in the earliest iNKT precursors. We find that iNKT cells expressing the lower affinity TCRVbeta8 are proportionally overrepresented in the absence of Fra-2, indicating altered selection of iNKT cells. There is also widespread dysregulation of AP-1-directed gene expression. In the periphery, mature Fra-2-deficient iNKT cells are able to participate in an immune response, but they have an altered response to Ag, showing increased expansion and producing increased amounts of IL-2 and IL-4 compared with their wild-type counterparts. Unusually, naive Fra-2-deficient T cells also rapidly produce IL-2 and IL-4 upon activation. Taken together, these data define Fra-2 as necessary for regulation of normal iNKT cell development and function, and they demonstrate the central role played by the AP-1 family in this lineage.
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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/Fos-Related Antigen-2,
http://linkedlifedata.com/resource/pubmed/chemical/Fosl2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-4,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor AP-1
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1550-6606
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
183
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2575-84
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pubmed:meshHeading |
pubmed-meshheading:19620306-Amino Acid Sequence,
pubmed-meshheading:19620306-Animals,
pubmed-meshheading:19620306-Cell Differentiation,
pubmed-meshheading:19620306-Cell Proliferation,
pubmed-meshheading:19620306-Fos-Related Antigen-2,
pubmed-meshheading:19620306-Gene Deletion,
pubmed-meshheading:19620306-Interleukin-2,
pubmed-meshheading:19620306-Interleukin-4,
pubmed-meshheading:19620306-Mice,
pubmed-meshheading:19620306-Mice, Inbred C57BL,
pubmed-meshheading:19620306-Mice, Knockout,
pubmed-meshheading:19620306-Mice, Transgenic,
pubmed-meshheading:19620306-Molecular Sequence Data,
pubmed-meshheading:19620306-Natural Killer T-Cells,
pubmed-meshheading:19620306-Thymus Gland,
pubmed-meshheading:19620306-Transcription Factor AP-1
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pubmed:year |
2009
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pubmed:articleTitle |
Aberrant selection and function of invariant NKT cells in the absence of AP-1 transcription factor Fra-2.
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pubmed:affiliation |
Section of Cell and Molecular Biology, Institute of Cancer Research, London, United Kingdom.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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