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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

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[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
2015-09-15
Citation
Journal of Immunology, 195(6), 2861-2869
Type
Article
Article Type
Article
Keywords
BiosynthesisCD8-Positive T-LymphocytesCD8+ T LymphocyteCell AdhesionCell AssayCell CultureCells, CulturedChemokine CX3CL1Chemokine ReceptorChemokine Receptor CX3CR1ChemotaxisControlled StudyCX3CR1 Protein, HumanDNA MethylationEffector CellEndothelium CellFractalkineGamma InterferonGene ExpressionGenetic AssociationGeneticsHumanHuman CellHumansImmune ResponseImmunologic MemoryImmunological MemoryImmunologyInterferon-GammaInterleukin-7 ReceptorInterleukin-7 Receptor AlphaInterleukin-7 Receptor, Alpha ChainLymphocyte MigrationMemory CellMetabolismMolecular DynamicsPriority JournalPromoter RegionPromoter Regions, GeneticProtein DeterminationProtein ExpressionProtein FunctionReceptors, ChemokineReceptors, Interleukin-7T-Lymphocyte SubsetsT Lymphocyte SubpopulationTumor Necrosis Factor-Alpha
ISSN
0022-1767
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-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.
URI
http://hdl.handle.net/20.500.11750/2846
DOI
10.4049/jimmunol.1500877
Publisher
American Association of Immunologists
Related Researcher
  • Author Hwang, Dae Hee Systems Biology and Medicine Lab
  • Research Interests Multilayered spatiotemporal networks; Regulatory motifs or pathways; Metabolite-protein networks; Network stochasticity; Proteomics and informatics
Files:
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Collection:
New BiologyETC1. Journal Articles


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