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- Title
Autophagy promotes T-cell survival through degradation of proteins of the cell death machinery.
- Authors
Kovacs, J R; Li, C; Yang, Q; Li, G; Garcia, I G; Ju, S; Roodman, D G; Windle, J J; Zhang, X; Lu, B
- 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.
- Subjects
CELL death; T cells; AUTOPHAGY; ENCEPHALOMYELITIS; LYMPHOCYTES
- Publication
Cell Death & Differentiation, 2012, Vol 19, Issue 1, p144
- ISSN
1350-9047
- Publication type
Article
- DOI
10.1038/cdd.2011.78