Autophagy in regulatory T cells: A double-edged sword in disease settings

Autophagy is an evolutionarily conserved catabolic process that directs cytoplasmic proteins, organelles and microbes to lysosomes for degradation. It not only represents an essential cell-intrinsic mechanism to protect against internal and external stresses but also shapes both innate and adaptive immunity. Regulatory T cells (Tregs) are a developmentally and functionally distinct T cell subpopulation engaged in sustaining immunological self-tolerance and homeostasis. There is compelling evidence that autophagy is actively regulated in Tregs and serves as a central signal-dependent controller for Tregs by restraining excessive apoptotic and metabolic activities. In this review, we discuss how autophagy modulates the stability and functionality of Tregs in different disease settings, and provide a perspective on how manipulation of autophagy enables better control of immune response by targeting the generation of Tregs and the maintenance of their stability.