The miR-17∼92a cluster of microRNAs is required for the fitness of Foxp3+ regulatory T cells

Abstract

By genetic inactivation of key microRNA biogenesis enzymes, we and others have previously demonstrated the critical requirement of the microRNA pathway for the differentiation and function of Foxp3+ regulatory T cells. In this study, we identified members of the miR-17∼92a cluster of microRNAs to be enriched in regulatory T cells. To investigate the function of this microRNA cluster, we deleted the gene specifically in Foxp3+ cells in mice. We found that miR-17∼92a is required for the fitness of regulatory T cells, and deficiency impacted at the level of apoptosis and proliferation of these cells. This led to a loss of Foxp3+ cells over time, particularly in competitive settings, and culminated in a range of immunologic perturbations. Thus, miR-17∼92a-target interactions are part of the essential microRNA networks that safeguard the regulatory T cell lineage. © 2014 Skinner et al.