期刊
EPIGENETICS
卷 8, 期 1, 页码 66-78出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/epi.23115
关键词
NKG2D receptor; KLRK1 gene; DNA methylation; H3K9 acetylation; cytotoxicity; curcumin
资金
- Spanish grants from the Red de Investigacion Renal (REDinREN)
- Instituto Carlos III [FIS PI08/0566, PI12/02587]
- Severo Ochoa fellowship (FICYT, Consejeria de Educacion y Ciencia del Principado de Asturias, Spain)
The human activating receptor NKG2D is mainly expressed by NK, NKT, gamma delta T and CD8(+) T cells and, under certain conditions, by CD4(+) T cells. This receptor recognizes a diverse family of ligands (MICA, MICB and ULBPs 1-6) leading to the activation of effector cells and triggering the lysis of target cells. The NKG2D receptor-ligand system plays an important role in the immune response to infections, tumors, transplanted graft and autoantigens. Elucidation of the regulatory mechanisms of NKG2D is therefore essential for therapeutic purposes. In this study, we speculate whether epigenetic mechanisms, such as DNA methylation and histone acetylation, participate in NKG2D gene regulation in T lymphocytes and NK cells. DNA methylation in the NKG2D gene was observed in CD4(+) T lymphocytes and T cell lines (Jurkat and HUT78), while this gene was unmethylated in NKG2D-positive cells (CD8(+) T lymphocytes, NK cells and NKL cell line) and associated with high levels of histone H3 lysine 9 acetylation (H3K9Ac). Treatment with the histone acetyltransferase (HA T) inhibitor curcumin reduces H3K9Ac levels in the NKG2D gene, downregulates NKG2D transcription and leads to a marked reduction in the lytic capacity of NKG2D-mediated NKL cells. These findings suggest that differential NKG2D expression in the different cell subsets is regulated by epigenetic mechanisms and that its modulation by epigenetic treatments might provide a new strategy for treating several pathologies.
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