Kato H, et al. - A study population including systemic lupus erythematosus (SLE) patients, was assessed to investigate if the mechanistic target of rapamycin (mTOR) is activated within regulatory T-cells (Tregs) and causes their depletion and dysfunction. Findings demonstrated that IL-21-driven mTOR activation is a pharmacologically targetable checkpoint of deficient autophagy that underlies Treg dysfunction in SLE.