Autophagy promotes T-cell survival through degradation of proteins of the cell death machinery

J. R. Kovacs, C. Li, Q. Yang, G. Li, I. G. Garcia, S. Ju, G. David Roodman, J. J. Windle, X. Zhang, B. Lu

Research output: Contribution to journalArticle

99 Citations (Scopus)

Abstract

Autophagy is implicated in regulating cell death in activated T cells, but the underlying mechanism is unclear. Here, we show that inhibition of autophagy via Beclin 1 gene deletion in T cells leads to rampant apoptosis in these cells upon TCR stimulation. Beclin 1-deficient mice fail to mount autoreactive T-cell responses and are resistant to experimental autoimmune encephalomyelitis. Compared with Th17 cells, Th1 cells are much more susceptible to cell death upon Beclin 1 deletion. Cell death proteins are highly increased in Beclin 1-deficient T cells and inhibition of caspases and genetic deletion of Bim reverse apoptosis. In addition, p62/sequestosome 1 binds to caspase-8 but does not control levels of procaspase-8 or other cell death-related proteins. These results establish a direct role of autophagy in inhibiting the programmed cell death through degradation of apoptosis proteins in activated T cells.

Original languageEnglish (US)
Pages (from-to)144-152
Number of pages9
JournalCell Death and Differentiation
Volume19
Issue number1
DOIs
StatePublished - Jan 2012
Externally publishedYes

Fingerprint

Autophagy
Proteolysis
Cell Survival
Cell Death
T-Lymphocytes
Caspase 8
Apoptosis
Th17 Cells
Th1 Cells
Autoimmune Experimental Encephalomyelitis
Gene Deletion
Caspases
Proteins
Beclin-1

Keywords

  • apoptosis
  • autophagy
  • Beclin 1
  • caspase
  • T cell
  • Th1 cell

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Autophagy promotes T-cell survival through degradation of proteins of the cell death machinery. / Kovacs, J. R.; Li, C.; Yang, Q.; Li, G.; Garcia, I. G.; Ju, S.; Roodman, G. David; Windle, J. J.; Zhang, X.; Lu, B.

In: Cell Death and Differentiation, Vol. 19, No. 1, 01.2012, p. 144-152.

Research output: Contribution to journalArticle

Kovacs, JR, Li, C, Yang, Q, Li, G, Garcia, IG, Ju, S, Roodman, GD, Windle, JJ, Zhang, X & Lu, B 2012, 'Autophagy promotes T-cell survival through degradation of proteins of the cell death machinery', Cell Death and Differentiation, vol. 19, no. 1, pp. 144-152. https://doi.org/10.1038/cdd.2011.78
Kovacs, J. R. ; Li, C. ; Yang, Q. ; Li, G. ; Garcia, I. G. ; Ju, S. ; Roodman, G. David ; Windle, J. J. ; Zhang, X. ; Lu, B. / Autophagy promotes T-cell survival through degradation of proteins of the cell death machinery. In: Cell Death and Differentiation. 2012 ; Vol. 19, No. 1. pp. 144-152.
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