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Autophagy enforces functional integrity of regulatory T cells by coupling environmental cues and metabolic homeostasis.
- Source :
-
Nature immunology [Nat Immunol] 2016 Mar; Vol. 17 (3), pp. 277-85. Date of Electronic Publication: 2016 Jan 25. - Publication Year :
- 2016
-
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.
- Subjects :
- Adenocarcinoma immunology
Adoptive Transfer
Animals
Apoptosis immunology
Autophagy immunology
Autophagy-Related Protein 5
Autophagy-Related Protein 7
Cell Line, Tumor
Colonic Neoplasms immunology
DNA Methylation
Flow Cytometry
Gene Expression Profiling
Gene Expression Regulation
Glycolysis
Homeostasis
Immunoblotting
Lymphocyte Activation immunology
Lymphocytes, Tumor-Infiltrating immunology
Mechanistic Target of Rapamycin Complex 1
Mice
Mice, Knockout
Neoplasm Transplantation
Real-Time Polymerase Chain Reaction
Up-Regulation
Apoptosis genetics
Autophagy genetics
Forkhead Transcription Factors genetics
Microtubule-Associated Proteins genetics
Multiprotein Complexes metabolism
Proto-Oncogene Proteins c-myc metabolism
T-Lymphocytes, Regulatory immunology
TOR Serine-Threonine Kinases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2916
- Volume :
- 17
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Nature immunology
- Publication Type :
- Academic Journal
- Accession number :
- 26808230
- Full Text :
- https://doi.org/10.1038/ni.3365