Journal of Clinical Immunology

, Volume 28, Issue 2, pp 139–146 | Cite as

DNA Methylation and the Expression of IL-4 and IFN-γ Promoter Genes in Patients with Bronchial Asthma

  • Nam-Hee Kwon
  • Jin-Seuk Kim
  • Jin-Young Lee
  • Mi-Jung Oh
  • Dong-Chull Choi
Article

Abstract

Although CpG methylation is thought to be a negative regulator of gene transcription, its relationship with cytokine expression remains unclear. Interleukin (IL)-4 and interferon (IFN)-γ are major cytokines that affect the differentiation of naïve CD4+ T lymphocytes into the Th1 and Th2 lineage. We used bisulfite deoxyribonucleic acid modification and sequencing to examine the relationship between CpG methylation and IL-4 and IFN-γ gene expression before and after allergen stimulation in human CD4+ T lymphocytes from sensitized hosts. In naïve cells, the CpGs in the promoter regions were methylated largely in both the IL-4 and IFN-γ genes. After Dermatophagoides pteronyssinus/Dermatophagoides farinae stimulation, the degree of unmethylation in the IL-4 gene increased in cells from patients with bronchial asthma. After phytohemagglutinin stimulation, the degree of unmethylation increased in cells from nonallergic control subjects. The concentration of IL-4 was strongly correlated with the degree of unmethylation in the patient group. These data suggest that CpGs located at −80 of the IL-4 gene and at −295, −186, and +122 of the IFN-γ gene have regulatory activities important for cytokine expression. We conclude that the stimulation of CD4+ T lymphocytes causes considerable increases in the degree of unmethylation and that in sensitized hosts, the extent of unmethylation correlates with the concentration of IL-4.

Keywords

Methylation IL-4 IFN-γ bronchial asthma 

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Nam-Hee Kwon
    • 1
  • Jin-Seuk Kim
    • 2
  • Jin-Young Lee
    • 1
  • Mi-Jung Oh
    • 1
  • Dong-Chull Choi
    • 1
  1. 1.Division of Allergies, Department of Medicine, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulSouth Korea
  2. 2.Genomic Research Center, Samsung Biomedical Research InstituteSungkyunkwan University School of MedicineSeoulSouth Korea

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