1. Profiling of CD4(+) T Cells with Epigenetic Immune Lineage Analysis
- Author
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Emma Ahlén Bergman, Fredrik Piehl, Vivianne Malmström, Ola Winqvist, Ludvig Linton, Michael Eberhardson, Per Marits, and Peter Janson
- Subjects
CD4-Positive T-Lymphocytes ,Multiple Sclerosis ,Regulatory T cell ,T cell ,Immunology ,Biology ,Epigenesis, Genetic ,Arthritis, Rheumatoid ,TCIRG1 ,03 medical and health sciences ,Interleukin 21 ,Th2 Cells ,0302 clinical medicine ,Immune system ,medicine ,Humans ,Immunology and Allergy ,Cytotoxic T cell ,Cell Lineage ,IL-2 receptor ,Cells, Cultured ,030304 developmental biology ,0303 health sciences ,Gene Expression Profiling ,Interleukin-17 ,DNA Methylation ,Th1 Cells ,3. Good health ,Cell biology ,medicine.anatomical_structure ,DNA methylation ,Cytokines ,030217 neurology & neurosurgery ,Transcription Factors - 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.
- Published
- 2011
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