| First Author | Plaza-Sirvent C | Year | 2017 |
| Journal | Cell Rep | Volume | 18 |
| Issue | 1 | Pages | 12-22 |
| PubMed ID | 28052242 | Mgi Jnum | J:251487 |
| Mgi Id | MGI:6102992 | Doi | 10.1016/j.celrep.2016.12.022 |
| Citation | Plaza-Sirvent C, et al. (2017) c-FLIP Expression in Foxp3-Expressing Cells Is Essential for Survival of Regulatory T Cells and Prevention of Autoimmunity. Cell Rep 18(1):12-22 |
| abstractText | Regulatory T (Treg) cells are critical for the shutdown of immune responses and have emerged as valuable targets of immunotherapies. Treg cells can rapidly proliferate; however, the homeostatic processes that limit excessive Treg cell numbers are poorly understood. Here, we show that, compared to conventional T cells, Treg cells have a high apoptosis rate ex vivo correlating with low c-FLIP expression. Treg-specific deletion of c-FLIP in mice resulted in fatal autoimmune disease of a scurfy-like phenotype characterized by absent peripheral Treg cells, activation of effector cells, multi-organ immune cell infiltration, and premature death. Surprisingly, blocking CD95L did not rescue Treg survival in vivo, suggesting additional survival functions of c-FLIP in Treg cells in addition to its classical role in the inhibition of death receptor signaling. Thus, our data reveal a central role for c-FLIP in Treg cell homeostasis and prevention of autoimmunity. |
