1. Profiling of CD4+ T Cells with Epigenetic Immune Lineage Analysis.
- Author
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Janson, Peter C. J., Linton, Ludvig Bernt, Bergman, Emma Ahlén, Marits, Per, Eberhardson, Michael, Piehl, Fredrik, Malmström, Vivianne, and Winqvist, Ola
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IMMUNE response , *MOLECULAR immunology , *GENETIC regulation , *T cell differentiation , *CYTOKINES , *CELL communication , *RHEUMATOID arthritis , *MULTIPLE sclerosis - Abstract
Proper transcriptional control of pro- and anti-inflammatory responses of the immune system is important for a fine-tuned balance between protection and tolerance. Emerging evidence suggests a key role for epigenetic regulation in governing the Th cell differentiation, where effector cytokines direct the overall immune response. In this study, we describe a method to pinpoint the location of isolated human CD4+ T cells on any T cell effector axis based on specific CpG methylation of cytokine and transcription factor loci. We apply the method on CD4+ cells obtained from rheumatoid arthritis and multiple sclerosis patients and show that synovial fluid infiltrating CD4+ T cells are committed toward both Th1 and regulatory T cell phenotype, whereas the Th2 response is suppressed. Furthermore, we show that the IL-17A gene is regulated by promoter methylation and that Th17 commitment is not a common feature in the inflamed joints of rheumatoid arthritis patients. We conclude that the method described in this paper allows for accurate profiling of Th lineage commitment in ex vivo-isolated CD4+ T cells. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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