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
SCIE
SCOPUS
- 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
- Authors
- Shin, MS; You, S; Kang, YN; Lee, N; Yoo, SA; Park, K; Kang, KS; Kim, SH; Mohanty, S; Shaw, AC; Montgomery, RR; Hwang, D; Kang, I
- Date Issued
- 2015-09-15
- Publisher
- American Association of Immunologists
- 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.
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/36215
- DOI
- 10.4049/JIMMUNOL.1500877
- ISSN
- 0022-1767
- Article Type
- Article
- Citation
- Journal of Immunology, vol. 195, no. 6, page. 2861 - 2869, 2015-09-15
- Files in This Item:
-
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.