- Top of page
- The role of epigenetics in the early life immune programming
- IFNγ production during early life and the risk of allergic disease
- IFNγ gene expression is regulated by epigenetic mechanisms
- Microbial exposure and the risk of allergic disease
- Does microbial exposure modify demethylation of the IFNγ gene?
- Proposed disease pathway
- Theoretical and practical issues relevant to investigating these hypotheses
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 (IFNγ) response during infancy is an important determinant of the risk of allergic disease, (2) expression of the IFNγ gene in naïve T-cells is regulated by epigenetic mechanisms, and (3) failure to up-regulate IFNγ 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 IFNγ gene of naive T-cells.