Polycomb repressive complex 2 is a critical mediator of allergic inflammation

Abstract

Strategies that intervene with the development of immune-mediated diseases are urgently needed, as current treatments mostly focus on alleviating symptoms rather than reversing the disease. Targeting enzymes involved in epigenetic modifcations to chromatin represents an alternative strategy that has the potential to perturb the function of the lymphocytes that drive the immune response. Here, we report that 2 major epigenetic silencing pathways are increased after T cell activation. By specifc inactivation of these molecules in the T cell compartment in vivo, we demonstrate that the polycomb repressive complex 2 (PRC2) is essential for the generation of allergic responses. Furthermore, we show that small-molecule inhibition of the PRC2 methyltransferase, enhancer of zeste homolog 2 (Ezh2), reduces allergic inflammation in mice. Therefore, by systematically surveying the pathways involved in epigenetic gene silencing we have identifed Ezh2 as a target for the suppression of allergic disease.