title: Microbial exposure, interferon gamma gene demethylation in naïve T-cells, and the risk of allergic disease.
abstract: The period of immune programming during early life presents a critical window of opportunity for the prevention of allergic diseases. There is mounting evidence that inappropriate immune programming may involve disruption of specific epigenetic modifications (switches) at immune-related genes. This novel area of research has great potential, as epigenetic changes are known to be sensitive to environmental factors and may therefore provide a mechanistic link for the observed association between specific environmental cues, faulty immune development, and the risk of allergic disease. In addition, the dynamic and potentially reversible nature of epigenetic modifications offers potentially novel targets for therapeutic and/or preventative interventions. We review the evidence that (1) failure to up-regulate the interferon gamma (IFNgamma) response during infancy is an important determinant of the risk of allergic disease, (2) expression of the IFNgamma gene in naïve T-cells is regulated by epigenetic mechanisms, and (3) failure to up-regulate IFNgamma gene expression of naïve T-cells associated with low early life microbial exposure. Taken together, these lines of evidence suggest that low microbial exposure during early life increases the risk of allergic disease by reducing demethylation (activation) of the IFNgamma gene of naive T-cells.
authors.affiliation: Child Health Research Unit, Barwon Health, Geelong, Victoria, Australia.
authors.forename: P J
authors.initials: PJ
authors.lastname: Vuillermin
authors.forename: A-L
authors.initials: AL
authors.lastname: Ponsonby
authors.forename: R
authors.initials: R
authors.lastname: Saffery
authors.forename: M L
authors.initials: ML
authors.lastname: Tang
authors.forename: J A
authors.initials: JA
authors.lastname: Ellis
authors.forename: P
authors.initials: P
authors.lastname: Sly
authors.forename: P
authors.initials: P
authors.lastname: Holt
mesh_terms: D019175:DNA Methylation; D044127:Epigenesis, Genetic / Q000276:immunology*; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics* / Q000276:immunology* / Q000382:microbiology*; D007371:Interferon-gamma / Q000235:genetics*; D012307:Risk Factors; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D007371:Interferon-gamma