Mechanistic target of rapamycin inhibitors (mTORi) have a complex immunoregulatory profile in both animal models and transplant patients. Studies suggest that mTORi act as tolerance-supporting and regulatory T cell (Treg)-promoting immunosuppressants. Yet proinflammatory influences on myeloid dendritic cells have been established. Insight is needed into the impact of mTORi on immune cells. Stallone et al. describe a clinical study identifying a potential immunoregulatory pathway involving plasmacytoid dendritic cells and Tregs in renal transplant patients on mTORi.