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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2010-10-21
pubmed:abstractText
The active vitamin A metabolite retinoic acid (RA) imprints gut-homing specificity on lymphocytes upon activation by inducing the expression of ?4?7 integrin and CCR9. RA receptor (RAR) activation is essential for their expression, whereas retinoid X receptor (RXR) activation is not essential for ?4?7 expression. However, it remains unclear whether RXR activation affects the RA-dependent CCR9 expression on T cells and their gut homing. The major physiological RA, all-trans-RA, binds to RAR but not to RXR at physiological concentrations. Cell-surface CCR9 expression was often induced on a limited population of murine naive CD4(+) T cells by all-trans-RA or the RAR agonist Am80 alone upon CD3/CD28-mediated activation in vitro, but it was markedly enhanced by adding the RXR agonist PA024 or the RXR-binding environmental chemicals tributyltin and triphenyltin. Accordingly, CD4(+) T cells treated with the combination of all-trans-RA and tributyltin migrated into the small intestine upon adoptive transfer much more efficiently than did those treated with all-trans-RA alone. Furthermore, naive TCR transgenic CD4(+) T cells transferred into wild-type recipients migrated into the small intestinal lamina propria following i.p. injection of Ag, and the migration was enhanced by i.p. injection of PA024. We also show that PA024 markedly enhanced the all-trans-RA-induced CCR9 expression on naturally occurring naive-like regulatory T cells upon activation, resulting in the expression of high levels of ?4?7, CCR9, and Foxp3. These results suggest that RXR activation enhances the RAR-dependent expression of CCR9 on T cells and their homing capacity to the small intestine.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1550-6606
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
185
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5289-99
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Efficient induction of CCR9 on T cells requires coactivation of retinoic acid receptors and retinoid X receptors (RXRs): exaggerated T Cell homing to the intestine by RXR activation with organotins.
pubmed:affiliation
Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University, Kagawa, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't