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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
- 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
- Shin, MS[Shin, Min Sun]; You, S[You, Sungyong]; Kang, YN[Kang, Youna]; Lee, N[Lee, Naeun]; Yoo, SA[Yoo, Seung-Ah]; Park, K[Park, Kieyoung]; Kang, KS[Kang, Ki Soo]; Kim, SH[Kim, Sang Hyun]; Mohanty, S[Mohanty, Subhasis]; Shaw, AC[Shaw, Albert C.]; Montgomery, RR[Montgomery, Ruth R.]; Hwang, D[Hwang, Daehee]; Kang, I[Kang, Insoo]
- DGIST Authors
- Hwang, D[Hwang, Daehee]
- Issue Date
- Journal of Immunology, 195(6), 2861-2869
- Article Type
- Biosynthesis; CD8-Positive T-Lymphocytes; CD8+ T Lymphocyte; Cell Adhesion; Cell Assay; Cell Culture; Cells, Cultured; Chemokine CX3CL1; Chemokine Receptor; Chemokine Receptor CX3CR1; Chemotaxis; Controlled Study; CX3CR1 Protein, Human; DNA Methylation; Effector Cell; Endothelium Cell; Fractalkine; Gamma Interferon; Gene Expression; Genetic Association; Genetics; Human; Human Cell; Humans; Immune Response; Immunologic Memory; Immunological Memory; Immunology; Interferon-Gamma; Interleukin-7 Receptor; Interleukin-7 Receptor Alpha; Interleukin-7 Receptor, Alpha Chain; Lymphocyte Migration; Memory Cell; Metabolism; Molecular Dynamics; Priority Journal; Promoter Region; Promoter Regions, Genetic; Protein Determination; Protein Expression; Protein Function; Receptors, Chemokine; Receptors, Interleukin-7; T-Lymphocyte Subsets; T Lymphocyte Subpopulation; Tumor Necrosis Factor-Alpha
- 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-7Rα. 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-7Rαlow and IL-7Rαhigh EM CD8+ T cells. In particular, IL-7Rαlow EMCD8+ T cells had increased expression of CX3CR1 along with decreased DNA methylation in the CX3CR1 gene promoter compared with IL-7Rαhigh EM CD8+ T cells. Altering the DNA methylation status of the CX3CR1 gene promoter changed its activity and gene expression. IL-7Rαlow EM CD8+ T cells had an increased migratory capacity to the CX3CR1 ligand fractalkine compared with IL-7Rαhigh EM CD8+ T cells, suggesting an important biological outcome of the differential expression of CX3CR1. Moreover, IL-7Rαlow EM CD8+ T cells induced fractalkine expression on endothelial cells by producing IFN-γ and TNF-α, forming an autocrine amplification loop. Overall, our study shows the role of DNA methylation in generating unique cellular traits in human IL-7Rαlow and IL-7Rαhigh EM CD8+ T cells, including differential expression of CX3CR1, as well as potential biological implications of this differential expression. © 2015 by The American Association of Immunologists, Inc.
- American Association of Immunologists
- Related Researcher
Hwang, Dae Hee
Systems Biology and Medicine Lab
Multilayered spatiotemporal networks; Regulatory motifs or pathways; Metabolite-protein networks; Network stochasticity; Proteomics and informatics
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