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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
10
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pubmed:dateCreated |
2010-5-20
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pubmed:abstractText |
Th17 cells are major effector T cells in the intestine, but the regulation of their tissue tropism within the gut is poorly understood. We investigated the roles of vitamin A and retinoic acid in generation of inflammatory Th17 cells with distinct tissue tropisms within the intestine. We found that Th17 cells with distinct tissue tropisms and pathogenic activities are generated depending on the available concentration of retinoic acid (RA). In contrast to the widespread perception that RA would suppress the generation of Th17 cells, we provide evidence that RA is actually required for generation of Th17 cells with specific tissue tropisms within the gut. Th17 cells induced at suboptimal serum concentrations of RA migrated and induced moderate inflammation mainly in the large intestine, whereas the Th17 cells induced with optimal levels of exogenous RA (approximately 10 nM) migrated to the small intestine and induced more severe inflammation. The Th17 cells, induced in the presence or absence of RA, differentially expressed the trafficking receptors CCR9 and alpha4beta7. CCR9 is required for Th17 cell migration to the small intestine, whereas alpha4beta7 is required for the migration of Th17 cells throughout the whole intestine. Our results identified RA as a major signal that regulates the generation of gut Th17 cells with distinct capacities in migration and inflammatory activities. The results indicate also that specific gut tropism of Th17 cells is determined by the combination of trafficking receptors regulated by the RA signal.
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pubmed:grant |
http://linkedlifedata.com/resource/pubmed/grant/1R01AI074745,
http://linkedlifedata.com/resource/pubmed/grant/1R01DK076616,
http://linkedlifedata.com/resource/pubmed/grant/1R56AI080769,
http://linkedlifedata.com/resource/pubmed/grant/R01 AI074745-01A1,
http://linkedlifedata.com/resource/pubmed/grant/R01 AI074745-02,
http://linkedlifedata.com/resource/pubmed/grant/R01 AI074745-03,
http://linkedlifedata.com/resource/pubmed/grant/R01 AI074745-04,
http://linkedlifedata.com/resource/pubmed/grant/R01 AI080769-01A2,
http://linkedlifedata.com/resource/pubmed/grant/R01 AI080769-02,
http://linkedlifedata.com/resource/pubmed/grant/R01 DK076616-01A1,
http://linkedlifedata.com/resource/pubmed/grant/R01 DK076616-02,
http://linkedlifedata.com/resource/pubmed/grant/R01 DK076616-03,
http://linkedlifedata.com/resource/pubmed/grant/R01 DK076616-04,
http://linkedlifedata.com/resource/pubmed/grant/R21 AI063064-01A1,
http://linkedlifedata.com/resource/pubmed/grant/R21 AI063064-02,
http://linkedlifedata.com/resource/pubmed/grant/R56 AI080769-01A1,
http://linkedlifedata.com/resource/pubmed/grant/Z01 HD001803-14,
http://linkedlifedata.com/resource/pubmed/grant/Z01 HD001803-15,
http://linkedlifedata.com/resource/pubmed/grant/Z99 HD999999,
http://linkedlifedata.com/resource/pubmed/grant/ZIA HD001803-16,
http://linkedlifedata.com/resource/pubmed/grant/ZIA HD001803-17
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1550-6606
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
184
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5519-26
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pubmed:dateRevised |
2011-9-29
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pubmed:meshHeading |
pubmed-meshheading:20400707-Animals,
pubmed-meshheading:20400707-Cell Differentiation,
pubmed-meshheading:20400707-Cells, Cultured,
pubmed-meshheading:20400707-Chemotaxis, Leukocyte,
pubmed-meshheading:20400707-Inflammation,
pubmed-meshheading:20400707-Interleukin-17,
pubmed-meshheading:20400707-Intestine, Small,
pubmed-meshheading:20400707-Lymphocyte Count,
pubmed-meshheading:20400707-Mice,
pubmed-meshheading:20400707-Mice, Inbred AKR,
pubmed-meshheading:20400707-Mice, Inbred C57BL,
pubmed-meshheading:20400707-Mice, Knockout,
pubmed-meshheading:20400707-Mice, Transgenic,
pubmed-meshheading:20400707-Receptors, Lymphocyte Homing,
pubmed-meshheading:20400707-Severity of Illness Index,
pubmed-meshheading:20400707-T-Lymphocytes, Helper-Inducer,
pubmed-meshheading:20400707-Tretinoin
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pubmed:year |
2010
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pubmed:articleTitle |
Retinoic acid determines the precise tissue tropism of inflammatory Th17 cells in the intestine.
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pubmed:affiliation |
Laboratory of Immunology and Hematopoiesis, Department of Comparative Pathobiology, Purdue Cancer Center, Purdue University, West Lafayette, IN 47907, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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