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

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.

SUBMITTER: Kovacs JR

PROVIDER: S-EPMC3252822 | biostudies-other | 2012 Jan

REPOSITORIES: biostudies-other

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

Kovacs J R JR Li C C Yang Q Q Li G G Garcia I G IG Ju S S Roodman D G DG Windle J J JJ Zhang X X Lu B B

Cell death and differentiation 20110610 1

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 ...[more]

PMID: 21660048

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