| First Author | Ch'en IL | Year | 2011 |
| Journal | J Exp Med | Volume | 208 |
| Issue | 4 | Pages | 633-41 |
| PubMed ID | 21402742 | Mgi Jnum | J:177328 |
| Mgi Id | MGI:5294742 | Doi | 10.1084/jem.20110251 |
| Citation | Ch'en IL, et al. (2011) Mechanisms of necroptosis in T cells. J Exp Med 208(4):633-41 |
| abstractText | Cell populations are regulated in size by at least two forms of apoptosis. More recently, necroptosis, a parallel, nonapoptotic pathway of cell death, has been described, and this pathway is invoked in the absence of caspase 8. In caspase 8-deficient T cells, necroptosis occurs as the result of antigen receptor-mediated activation. Here, through a genetic analysis, we show that necroptosis in caspase 8-deficient T cells is related neither to the programmed necrosis as defined by the requirement for mitochondrial cyclophilin D nor to autophagy as defined by the requirement for autophagy-related protein 7. Rather, survival of caspase 8-defective T cells can be completely rescued by loss of receptor-interacting serine-threonine kinase (Ripk) 3. Additionally, complementation of a T cell-specific caspase 8 deficiency with a loss of Ripk3 gives rise to lymphoproliferative disease reminiscent of lpr or gld mice. In conjunction with previous work, we conclude that necroptosis in antigen-stimulated caspase 8-deficient T cells is the result of a novel Ripk1- and Ripk3-mediated pathway of cell death. |
