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

作者：Weil, Jun; Long, Lingyun; Yang, Kai; Guyl, Cliff; Shresthal, Sharad; Chen, Zuojia; Wu, Chuan; Voge, Peter; Neale, Geoffrey; Green, Douglas R.; Chi, Hongbo^*

来源：Nature Immunology, 2016, 17(3): 277-285.

DOI：10.1038/ni.3365

• TRANSCRIPTION FACTOR FOXP3
• CIS-ELEMENT
• DIFFERENTIATION
• EFFECTOR
• ACTIVATION
• SURVIVAL
• INSTABILITY
• INHIBITION
• EXPRESSION
• GENERATION

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.

• 出版日期2016-3
• 单位上海生物信息技术研究中心