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Down-regulation of interleukin-2 production by CD4(+) T cells expressing TIM-3 through suppression of NFAT dephosphorylation and AP-1 transcription

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dc.contributor.authorLee, MJ-
dc.contributor.authorWoo, MY-
dc.contributor.authorChwae, YJ-
dc.contributor.authorKwon, MH-
dc.contributor.authorKim, K-
dc.contributor.authorPark, S-
dc.date.accessioned2013-04-23T06:06:53Z-
dc.date.available2013-04-23T06:06:53Z-
dc.date.issued2012-
dc.identifier.issn0171-2985-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/7879-
dc.description.abstractTIM-3 is expressed by TH1 cells and negatively regulates cytokine production by these cells. The aim of the present study was to explore the mechanisms by which IL-2 production is suppressed in TIM-3-expressing T cells. First, the activity of two transcription factors that bind to the IL-2 promoter was examined in Jurkat T cells expressing TIM-3. Both AP-1 and NFAT activity were reduced in TIM-3-expressing cells stimulated with a phorbol ester and a calcium ionophore. At the same time, expression of the AP-1 components, c-Fos and c-Jun, was induced to a lesser extent in stimulated human primary CD4(+) T cells expressing high levels of TIM-3 than in those expressing low levels of TIM-3. Furthermore, TIM-3-expression inhibited the stimulation-induced dephosphorylation and nuclear translocation of NFAT in Jurkat T cells and primary CD4(+) T cells. Finally, the cytoplasmic tail of TIM-3 was required for the suppression of IL-2 production and for AP-1 and NFAT activation. Taken together, these results suggest that IL-2 production by T cells may be downregulated by TIM-3-mediated signals, leading to suppression of NFAT dephosphorylation and AP-1 transcription.-
dc.language.isoen-
dc.subject.MESHActive Transport, Cell Nucleus-
dc.subject.MESHCD4-Positive T-Lymphocytes-
dc.subject.MESHCell Nucleus-
dc.subject.MESHGene Expression Regulation-
dc.subject.MESHHumans-
dc.subject.MESHInterleukin-2-
dc.subject.MESHJurkat Cells-
dc.subject.MESHLymphocyte Activation-
dc.subject.MESHMembrane Proteins-
dc.subject.MESHNFATC Transcription Factors-
dc.subject.MESHPhosphorylation-
dc.subject.MESHProtein Transport-
dc.subject.MESHTranscription Factor AP-1-
dc.subject.MESHTranscription, Genetic-
dc.titleDown-regulation of interleukin-2 production by CD4(+) T cells expressing TIM-3 through suppression of NFAT dephosphorylation and AP-1 transcription-
dc.typeArticle-
dc.identifier.pmid22445722-
dc.identifier.urlhttp://linkinghub.elsevier.com/retrieve/pii/S0171-2985(12)00016-2-
dc.contributor.affiliatedAuthor이, 미진-
dc.contributor.affiliatedAuthor최, 용준-
dc.contributor.affiliatedAuthor권, 명희-
dc.contributor.affiliatedAuthor김, 경민-
dc.contributor.affiliatedAuthor박, 선-
dc.type.localJournal Papers-
dc.identifier.doi10.1016/j.imbio.2012.01.012-
dc.citation.titleImmunobiology-
dc.citation.volume217-
dc.citation.number10-
dc.citation.date2012-
dc.citation.startPage986-
dc.citation.endPage995-
dc.identifier.bibliographicCitationImmunobiology, 217(10). : 986-995, 2012-
dc.identifier.eissn1878-3279-
dc.relation.journalidJ001712985-
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Microbiology
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