Early-life immune programming

Epigenetic mechanisms link the fixed genome, the highly variable external environment, and gene transcription [29]. One mechanism, DNA methylation, plays an important role in the functioning of the immune system, and immune cell differentiation. Environmental exposure to lipopolysaccharides, through epigenetic modifications, has a strong influence on the immune system[30, 31].For instance,during the sensitive perinatal period transient or seemingly insignificant environmental changes (e.g. maternal infection) are major risk factors for later pathology [32-34].Our preliminary datashows thatLPS exposure at postnatal day 7 induced a lifelong programming of the cytokine response, which wasassociated with global methylation changes throughout the hematopoietic compartment. The goals of this project are twofold: determining the mechanisms underlying the lifelong immune programing, and to demonstrate proof of concept for thereversibility of epigenetic immune and endocrine system programming.