Autophagy enforces functional integrity of regulatory T cells by coupling environmental cues and metabolic homeostasis

Regulatory T (T reg ) cells have a distinct cellular metabolism compared to effector T cells. Chi and colleagues show that autophagy is required to maintain the functional integrity and metabolic homeostasis of T reg cells in the face of inflammatory environmental cues. Regulatory T (T reg ) cells respond to immune and inflammatory signals to mediate immunosuppression, but how the functional integrity of T reg cells is maintained under activating environments is unclear. Here we show that autophagy is active in T reg cells and supports their lineage stability and survival fitness. T reg cell–specific deletion of Atg7 or Atg5 , two essential genes in autophagy, leads to loss of T reg cells, greater tumor resistance and development of inflammatory disorders. Atg7-deficient T reg cells show increased apoptosis and readily lose expression of the transcription factor Foxp3, especially after activation. Mechanistically, autophagy deficiency upregulates metabolic regulators mTORC1 and c-Myc and glycolysis, which contribute to defective T reg function. Therefore, autophagy couples environmental signals and metabolic homeostasis to protect lineage and survival integrity of T reg cells in activating contexts.