CpG methylation patterns in the IFN gamma promoter in naive T cells: variations during Th1 and Th2 differentiation and between atopics and non-atopics

White, Gregory P., Hollams, Elysia M., Yerkovich, Stephanie T., Bosco, Anthony, Holt, Barbara J., Bassami, Mohammad R., Kusel, Merci, Sly, Peter D. and Holt, Patrick G. (2006) CpG methylation patterns in the IFN gamma promoter in naive T cells: variations during Th1 and Th2 differentiation and between atopics and non-atopics. Pediatric Allergy and Immunology, 17 8: 557-564. doi:10.1111/j.1399-3038.2006.00465.x


Author White, Gregory P.
Hollams, Elysia M.
Yerkovich, Stephanie T.
Bosco, Anthony
Holt, Barbara J.
Bassami, Mohammad R.
Kusel, Merci
Sly, Peter D.
Holt, Patrick G.
Title CpG methylation patterns in the IFN gamma promoter in naive T cells: variations during Th1 and Th2 differentiation and between atopics and non-atopics
Formatted title
CpG methylation patterns in the IFNγ promoter in naive T cells: variations during Th1 and Th2 differentiation and between atopics and non-atopics
Journal name Pediatric Allergy and Immunology   Check publisher's open access policy
ISSN 0905-6157
1399-3038
Publication date 2006-12
Sub-type Article (original research)
DOI 10.1111/j.1399-3038.2006.00465.x
Volume 17
Issue 8
Start page 557
End page 564
Total pages 8
Place of publication Oxford, United Kingdom
Publisher Wiley-Blackwell Publishing
Language eng
Formatted abstract
Interferon-γ (IFNγ) gene expression is tightly regulated in early life, and exaggerated negative control of IFNγ production in CD4+ T cells has been associated with risk for subsequent development of atopy. Recent studies have demonstrated hypermethylation of CpG sites in the IFNγ promoter in neonates, a mechanism which in mice leads to strong suppression of IFNγ gene transcription. In the present study, the methylation status of six CpG sites in the proximal promoter of the human IFNγ gene was determined by bisulphite sequencing. Cell populations studied were Th1 or Th2 polarized cell lines derived from neonatal and adult CD4+/CD45RA+ T cells, CD4+ and CD8+ naive T cells from cord blood of children followed to outcome age 2 for assessment of atopy status, and CD4+ and CD8+ naive T cells from 6 yr old and adult atopics and controls. We demonstrate that in vitro differentiation of CD4+ T cells down the Th1 pathway (but not the Th2 pathway) is accompanied by progressive demethylation of CpG sites in the IFNγ promoter, which is most marked in neonatal cells. Atopy development by age 2 was not associated with variations in methylation patterns in cord blood T cells. However, IFNγ promoter methylation was reduced in CD8 + T cells from atopic children in the age range in which hyperproduction of IFNγ as recently been identified as a common feature of the atopic phenotype. The findings demonstrate the potency of IFNγ promoter methylation as a mechanism for control of human IFNγ gene expression, particularly during early life. Differential regulation of IFNγ promoter methylation in T cells may be an important contributory factor in atopy development in childhood, and this possibility warrants further detailed investigation.
Keyword IFN gamma
Methylation
Helper T cell
CpG
Atopy
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
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Created: Wed, 17 Nov 2010, 11:57:50 EST