Document Detail


Canonical autophagy dependent on the class III phosphoinositide-3 kinase Vps34 is required for naive T-cell homeostasis.
MedLine Citation:
PMID:  22592798     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The homeostasis of naive T cells is essential for protective immunity against infection, but the cell-intrinsic molecular mechanisms that control naïve T-cell homeostasis are poorly understood. Genetic ablation in lower organisms has revealed a critical role for Vps34, an evolutionary conserved class III phosphoinositide-3 kinase (PI3K), in regulating endocytosis and autophagy; however, the physiological function of Vps34 in the immune system, especially in T cells, is unclear. Here we report that Vps34 is required for the maintenance of naïve T cells, acting in a cell-intrinsic manner. T-cell-specific deletion of the gene encoding Vps34 resulted in reduced stability of Vps15 and Beclin-1, components of the class III PI3K complex, and impaired autophagy in T cells. Vps34 was dispensable for T-cell development but important for the survival of naïve T cells. Vps34-deficient T cells showed increased mitochondrial mass and accumulation of reactive oxygen species, consistent with deficient removal of damaged mitochondria. Thus, Vps34-dependent canonical autophagy plays a critical role in maintaining T-cell homeostasis by promoting T-cell survival through quality control of mitochondria.
Authors:
Tim Willinger; Richard A Flavell
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-05-16
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  109     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-05-30     Completed Date:  2012-08-24     Revised Date:  2013-06-25    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  8670-5     Citation Subset:  IM    
Affiliation:
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis Regulatory Proteins / metabolism
Autophagy / genetics,  physiology*
Blotting, Western
CD4-Positive T-Lymphocytes / cytology,  metabolism
CD8-Positive T-Lymphocytes / cytology,  metabolism
Cell Survival / genetics,  physiology
Cells, Cultured
Class III Phosphatidylinositol 3-Kinases / genetics,  metabolism*
Flow Cytometry
Homeostasis / genetics,  physiology*
Mice
Mice, Inbred C57BL
Mice, Knockout
Mitochondria / metabolism
Reactive Oxygen Species / metabolism
T-Lymphocytes / cytology,  metabolism*
Vacuolar Sorting Protein VPS15 / metabolism
Grant Support
ID/Acronym/Agency:
//Howard Hughes Medical Institute
Chemical
Reg. No./Substance:
0/Apoptosis Regulatory Proteins; 0/Becn1 protein, mouse; 0/Reactive Oxygen Species; EC 2.7.1.137/Class III Phosphatidylinositol 3-Kinases; EC 2.7.11.1/Vacuolar Sorting Protein VPS15
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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