DNA Methylation Regulates the Differential Expression of CX3CR1 on Human IL-7R alpha(low) and IL-7R alpha(high) Effector Memory CD8(+) T Cells with Distinct Migratory Capacities to the Fractalkine
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Title
- DNA Methylation Regulates the Differential Expression of CX3CR1 on Human IL-7R alpha(low) and IL-7R alpha(high) Effector Memory CD8(+) T Cells with Distinct Migratory Capacities to the Fractalkine
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Author(s)
- Shin, MS; You, S; Kang, YN; Lee, N; Yoo, SA; Park, K; Kang, KS; Kim, SH; Mohanty, S; Shaw, AC; Montgomery, RR; Daehee Hwang; Kang, I
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Publication Date
- 2015-09
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Journal
- JOURNAL OF IMMUNOLOGY, v.195, no.6, pp.2861 - 2869
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Publisher
- AMER ASSOC IMMUNOLOGISTS
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Abstract
- DNA methylation is an epigenetic mechanism that modulates gene expression in mammalian cells including T cells. Memory T cells are heterogeneous populations. Human effector memory (EM) CD8(+) T cells in peripheral blood contain two cell subsets with distinct traits that express low and high levels of the IL-7R alpha. However, epigenetic mechanisms involved in defining such cellular traits are largely unknown. In this study, we use genome-wide DNA methylation and individual gene expression to show the possible role of DNA methylation in conferring distinct traits of chemotaxis and inflammatory responses in human IL-7R alpha(low) and IL-7R alpha(high) EM CD8(+) T cells. In particular, IL-7R alpha(low) EMCD8(+)T cells had increased expression of CX3CR1 along with decreased DNA methylation in the CX3CR1 gene promoter compared with IL-7R alpha(high) EM CD8(+) T cells. Altering the DNA methylation status of the CX3CR1 gene promoter changed its activity and gene expression. IL-7R alpha(low) EM CD8(+) T cells had an increased migratory capacity to the CX3CR1 ligand fractalkine compared with IL-7R alpha(high) EM CD8(+) T cells, suggesting an important biological outcome of the differential expression of CX3CR1. Moreover, IL-7R alpha(low) EM CD8(+) T cells induced fractalkine expression on endothelial cells by producing IFN-gamma and TNF-alpha, forming an autocrine amplification loop. Overall, our study shows the role of DNA methylation in generating unique cellular traits in human IL-7R alpha(low) and IL-7R alpha(high) EM CD8(+) T cells, including differential expression of CX3CR1, as well as potential biological implications of this differential expression
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URI
- https://pr.ibs.re.kr/handle/8788114/1881
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DOI
- 10.4049/jimmunol.1500877
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ISSN
- 0022-1767
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