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

Abstract:

:Regulatory T (Treg) cells respond to immune and inflammatory signals to mediate immunosuppression, but how the functional integrity of Treg cells is maintained under activating environments is unclear. Here we show that autophagy is active in Treg cells and supports their lineage stability and survival fitness. Treg cell-specific deletion of Atg7 or Atg5, two essential genes in autophagy, leads to loss of Treg cells, greater tumor resistance and development of inflammatory disorders. Atg7-deficient Treg 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 Treg function. Therefore, autophagy couples environmental signals and metabolic homeostasis to protect lineage and survival integrity of Treg cells in activating contexts.

journal_name

Nat Immunol

journal_title

Nature immunology

authors

Wei J,Long L,Yang K,Guy C,Shrestha S,Chen Z,Wu C,Vogel P,Neale G,Green DR,Chi H

doi

10.1038/ni.3365

subject

Has Abstract

pub_date

2016-03-01 00:00:00

pages

277-85

issue

3

eissn

1529-2908

issn

1529-2916

pii

ni.3365

journal_volume

17

pub_type

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