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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

Authors
Lee, MJ  | Woo, MY | Chwae, YJ  | Kwon, MH  | Kim, K  | Park, S
Citation
Immunobiology, 217(10). : 986-995, 2012
Journal Title
Immunobiology
ISSN
0171-29851878-3279
Abstract
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

DOI
10.1016/j.imbio.2012.01.012
PMID
22445722
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Microbiology
Ajou Authors
권, 명희  |  김, 경민  |  박, 선  |  이, 미진  |  최, 용준
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