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题目:: 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)
状态:: 发布时间2011-12-13 , 更新时间 2016-11-25
期刊:: Cell Death Differ
摘要:: 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.
语言:: eng
DOI:

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