| First Author | Weinlich R | Year | 2013 |
| Journal | Cell Rep | Volume | 5 |
| Issue | 2 | Pages | 340-8 |
| PubMed ID | 24095739 | Mgi Jnum | J:203778 |
| Mgi Id | MGI:5528737 | Doi | 10.1016/j.celrep.2013.08.045 |
| Citation | Weinlich R, et al. (2013) Protective roles for caspase-8 and cFLIP in adult homeostasis. Cell Rep 5(2):340-8 |
| abstractText | Caspase-8 or cellular FLICE-like inhibitor protein (cFLIP) deficiency leads to embryonic lethality in mice due to defects in endothelial tissues. Caspase-8(-/-) and receptor-interacting protein kinase-3 (RIPK3)(-/-), but not cFLIP(-/-) and RIPK3(-/-), double-knockout animals develop normally, indicating that caspase-8 antagonizes the lethal effects of RIPK3 during development. Here, we show that the acute deletion of caspase-8 in the gut of adult mice induces enterocyte death, disruption of tissue homeostasis, and inflammation, resulting in sepsis and mortality. Likewise, acute deletion of caspase-8 in a focal region of the skin induces local keratinocyte death, tissue disruption, and inflammation. Strikingly, RIPK3 ablation rescues both phenotypes. However, acute loss of cFLIP in the skin produces a similar phenotype that is not rescued by RIPK3 ablation. TNF neutralization protects from either acute loss of caspase-8 or cFLIP. These results demonstrate that caspase-8-mediated suppression of RIPK3-induced death is required not only during development but also for adult homeostasis. Furthermore, RIPK3-dependent inflammation is dispensable for the skin phenotype. |
