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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

Lee, MJ; Woo, MY; Chwae, YJ; Kwon, MH; Kim, K; Park, S
Immunobiology, 217(10):986-995, 2012
Journal Title
TIM-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.
MeSH terms
Active Transport, Cell NucleusCD4-Positive T-Lymphocytes/*immunology/*metabolismCell Nucleus/metabolism*Gene Expression RegulationHumansInterleukin-2/*biosynthesis/geneticsJurkat CellsLymphocyte Activation/immunologyMembrane Proteins/*genetics/metabolismNFATC Transcription Factors/*metabolismPhosphorylationProtein TransportTranscription Factor AP-1/*geneticsTranscription, Genetic
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Journal Papers > School of Medicine / Graduate School of Medicine > Microbiology
AJOU Authors
이, 미진최, 용준권, 명희김, 경민박, 선
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