| First Author | Kovacs JR | Year | 2012 |
| Journal | Cell Death Differ | Volume | 19 |
| Issue | 1 | Pages | 144-52 |
| PubMed ID | 21660048 | Mgi Jnum | J:203090 |
| Mgi Id | MGI:5524203 | Doi | 10.1038/cdd.2011.78 |
| Citation | Kovacs JR, et al. (2012) Autophagy promotes T-cell survival through degradation of proteins of the cell death machinery. Cell Death Differ 19(1):144-52 |
| abstractText | 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. |
