Oxidative Stress, T Cell DNA Methylation and Lupus.
Lupus development is triggered when genetically predisposed people encounter environmental triggers that cause oxidative stress in the body such as UV light, silica, infections and cigarette smoke. However, it is unknown how this oxidative stress modified the immune system in order to create a Lupus flare up. The authors Li et al (2014) have previously found that inhibiting DNA methylation in immune T Cells by blocking the ERK signalling pathway is sufficient to alter the gene expression in cells that causes a lupus-like autoimmunity in mice. They also found T cells from patients with active lupus were found to have this decreased ERK signalling and therefore inhibited DNA methylation, which lead to an overexpression of genes normally supressed when levels of DNA methylation are normal.
In this study, they then tested whether the oxidising agents H2O2 or ONOO- decreased the correct functioning of T Cells ERK pathway signalling and DNA methylation levels. This resulted in demethylation and overexpression of T Cell genes found in active lupus. Results indeed found oxidative stress may contribute to human lupus flare ups by inhibiting T Cells and DNA methylation.