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

作者：Kovacs, J. R.; Li, C.; Yang, Q.; Li, G.; Garcia, I. G.; Ju, S.; Roodman, D. G.; Windle, J. J.; Zhang, X.; Lu, B.^*

来源：Cell Death and Differentiation, 2012, 19(1): 144-152.

DOI：10.1038/cdd.2011.78

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

• 出版日期2012-1
• 单位深圳市第三人民医院; 苏州大学; 河北医科大学