Epigenetic regulation of Th2 cytokine expression in atopic diseases

The immune response to allergens starts with stimulation of a naïve T helper (Th) cell and its differentiation into a Th2 cell, expressing the cytokines interleukin (IL)‐4, IL‐5 and IL‐13 responsible for the allergic response. The initial pattern of cytokine expression is retained during restimulati...

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Bibliographic Details
Published in:Tissue antigens 2008-08, Vol.72 (2), p.91-97
Main Authors: Van Panhuys, N., Le Gros, G., McConnell, M. J.
Format: Article
Language:English
Subjects:
acetylation
Animals
asthma
Chromatin - metabolism
Chromatin Assembly and Disassembly - genetics
Chromatin Assembly and Disassembly - physiology
Cytokines - genetics
Cytokines - metabolism
Epigenesis, Genetic - physiology
Gene Silencing - physiology
Humans
Hypersensitivity, Immediate - genetics
Hypersensitivity, Immediate - immunology
Hypersensitivity, Immediate - therapy
IL-4
methylation
Models, Biological
Quantitative Trait, Heritable
Th2
Th2 Cells - metabolism
Transcription Factors - metabolism
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Summary:The immune response to allergens starts with stimulation of a naïve T helper (Th) cell and its differentiation into a Th2 cell, expressing the cytokines interleukin (IL)‐4, IL‐5 and IL‐13 responsible for the allergic response. The initial pattern of cytokine expression is retained during restimulation and division of the Th2 cell to create a population of specific allergen‐responsive memory Th2 cells. Both, the coordinate cytokine expression and the inherited cytokine memory are specified by epigenetic mechanisms. Th2‐specific changes in chromatin configuration at the Th2 locus act locally to open DNA, allowing recruitment of transcriptional machinery and rapid induction of cytokine expression. Induction of the transcription factor GATA3 is critical to this process. Loss of DNA methylation at the Th2 locus during differentiation from a naïve Th cell correlates to increased histone acetylation, consistent with the expression of IL‐4, IL‐5 and IL‐13. The silencing of the Th2 locus in Th1 cells was associated with repressive histone methylation. These data indicate the formation of a ‘poised’ chromatin configuration at the Th2 locus that in combination with specific transcription factors specifies the cytokine repertoire in daughter cells and allows the immediate, rapid induction of cytokines by those cells in response to allergen.
ISSN:0001-2815
1399-0039
DOI:10.1111/j.1399-0039.2008.01068.x