Profiling of CD4+ T cells with epigenetic immune lineage analysis.
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.
Clinical Allergy Research Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Peter C J
PC
Janson
Ludvig Bernt
LB
Linton
Emma Ahlén
EA
Bergman
Per
P
Marits
Michael
M
Eberhardson
Fredrik
F
Piehl
Vivianne
V
Malmström
Ola
O
Winqvist
D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D019175:DNA Methylation / Q000276:immunology; D044127:Epigenesis, Genetic / Q000276:immunology*; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis / Q000235:genetics; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics
D016207:Cytokines; C508717:IL17A protein, human; D020381:Interleukin-17; D014157:Transcription Factors