Journal
CELL DEATH AND DIFFERENTIATION
Volume 19, Issue 1, Pages 144-152Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/cdd.2011.78
Keywords
T cell; Th1 cell; apoptosis; autophagy; caspase; Beclin 1
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Funding
- National Institutes of Health (NIH) [AI063496, P20 CA103730, T32 CA082084]
- NSFC [30528008]
- Eleven-Fifth Mega-Scientific Project on 'prevention and treatment of AIDS, viral hepatitis and other infectious diseases' [2008ZX10003-012]
- China Scholarship council [2010692006]
- NATIONAL CANCER INSTITUTE [P20CA103730, T32CA082084] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI063496] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [K01AR048854] Funding Source: NIH RePORTER
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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. Cell Death and Differentiation (2012) 19, 144-152; doi:10.1038/cdd.2011.78; published online 10 June 2011
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