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Regulation of TIM-3 expression in a human T cell line by tumor-conditioned media and cyclic AMP-dependent signaling

Authors
Yun, SJ; Lee, B; Komori, K; Lee, MJ; Lee, BG; Kim, K; Park, S
Citation
Molecular immunology, 105. : 224-232, 2019
Journal Title
Molecular immunology
ISSN
0161-58901872-9142
Abstract
T cell immunoglobulin and mucin domain-3 (TIM-3) expression increases in exhausted T cells, which inhibits T cell function. TIM-3 expression is supposedly up-regulated in tumor-bearing individuals via chronic antigenic stimulation of T cells. Considering the immunosuppressive nature of the tumor microenvironment, we investigated whether tumor-secreted molecules might enhance TIM-3 expression in Jurkat T cells. We observed that TIM-3 expression was increased by the activation of prostaglandin (PG) E2 and cyclic AMP (cAMP) signaling pathways. Adenylate cyclase activation led to protein kinase A (PKA)-dependent upregulation of the TIM-3 minimal promoter region and of upstream conserved non-coding sequences. TIM-3 expression in Jurkat T cells was increased by the exposure to breast tumor cell-conditioned media partially through the interaction between PGE2 and its receptor, EP4. Our results propose that tumor-secreted molecules such as PGE2, which activates PKA and EPAC, may regulate TIM-3 expression in T cells.
Keywords
CD4(+) T lymphocytesEPACHAVCR2PKAProstaglandin E(2)Transcription
MeSH terms
Cell Line, TumorCulture Media, Conditioned / pharmacologyCyclic AMP / immunology*Cyclic AMP / metabolismCyclic AMP-Dependent Protein Kinases / immunologyCyclic AMP-Dependent Protein Kinases / metabolismDinoprostone / metabolismDinoprostone / pharmacologyGene Expression Regulation / drug effectsGene Expression Regulation / immunology*Guanine Nucleotide Exchange Factors / immunologyGuanine Nucleotide Exchange Factors / metabolismHepatitis A Virus Cellular Receptor 2 / biosynthesisHepatitis A Virus Cellular Receptor 2 / immunology*HumansJurkat CellsMCF-7 CellsNeoplasms / immunology*Neoplasms / metabolismSecond Messenger Systems / drug effectsSecond Messenger Systems / immunology*
DOI
10.1016/j.molimm.2018.12.006
PMID
30554083
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Microbiology
AJOU Authors
이, 미진김, 경민박, 선
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