Journal
JOURNAL OF IMMUNOLOGY
Volume 186, Issue 1, Pages 92-102Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1000960
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Funding
- Swedish Research Council
- Swedish Cancer Society
- Cancer and Allergy Society
- Hedlunds Foundation
- Lundberg Foundation
- Gustav V. Foundation
- Selander Foundation
- Soderbergs Foundation
- European Community [HEALTH-F2-2008-223404]
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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. The Journal of Immunology, 2011, 186: 92-102.
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