Epigenetic regulation of killer immunoglobulin–like receptor expression in T cells
| العنوان: | Epigenetic regulation of killer immunoglobulin–like receptor expression in T cells |
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| المؤلفون: | Mingcan Yu, Jörg J. Goronzy, Cornelia M. Weyand, Guangjin Li |
| المصدر: | Blood. 114:3422-3430 |
| بيانات النشر: | American Society of Hematology, 2009. |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | Adult, CD4-Positive T-Lymphocytes, DNA (Cytosine-5-)-Methyltransferase 1, Male, Aging, Immunology, CD8-Positive T-Lymphocytes, Biology, Biochemistry, Epigenesis, Genetic, Interleukin 21, Humans, Cytotoxic T cell, Enhancer of Zeste Homolog 2 Protein, DNA (Cytosine-5-)-Methyltransferases, IL-2 receptor, Promoter Regions, Genetic, Aged, Interleukin 3, Aged, 80 and over, ZAP70, Polycomb Repressive Complex 2, Cell Biology, Hematology, DNA Methylation, Natural killer T cell, Molecular biology, DNA-Binding Proteins, DNA demethylation, Receptors, KIR2DL3, Interleukin 12, CpG Islands, Female, Transcription Factors |
| الوصف: | With increasing age, T cells gain expression of killer immunoglobulin–like receptors (KIRs) that transmit negative signals and dampen the immune response. KIR expression is induced in CD4 and CD8 T cells by CpG DNA demethylation suggesting epigenetic control. To define the mechanisms that underlie the age-associated preferential KIR expression in CD8 T cells, we examined KIR2DL3 promoter methylation patterns. With age, CD8 T cells developed a patchy and stochastic promoter demethylation even in cells that did not express the KIR2DL3-encoded CD158b protein; complete demethylation of the minimal KIR2DL3 promoter was characteristic for CD158b-expressing cells. In contrast, the promoter in CD4 T cells was fully methylated irrespective of age. The selectivity for CD8 T cells correlated with lower DNMT1 recruitment to the KIR2DL3 promoter which further diminished with age. In contrast, binding of the polycomb protein EZH2 known to be involved in DNMT1 recruitment was not different. Our data suggest that CD8 T cells endure increasing displacement of DNMT1 from the KIR promoter with age, possibly because of an active histone signature. The ensuing partial demethylation lowers the threshold for transcriptional activation and renders CD8 T cells more susceptible to express KIR, thereby contributing to the immune defect in the elderly. |
| تدمد: | 1528-0020 0006-4971 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::de609d6c7607f0e80bc6d125bb732874Test https://doi.org/10.1182/blood-2009-01-200170Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....de609d6c7607f0e80bc6d125bb732874 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15280020 00064971 |
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