| First Author | Imanishi T | Year | 2023 |
| Journal | Sci Adv | Volume | 9 |
| Issue | 4 | Pages | eadd6097 |
| PubMed ID | 36696505 | Mgi Jnum | J:344576 |
| Mgi Id | MGI:7431968 | Doi | 10.1126/sciadv.add6097 |
| Citation | Imanishi T, et al. (2023) RIPK1 blocks T cell senescence mediated by RIPK3 and caspase-8. Sci Adv 9(4):eadd6097 |
| abstractText | Receptor-interacting protein kinase 1 (RIPK1) regulates cell death and inflammation. Here, we show that T cell-specific RIPK1 deficiency in mice leads to the premature senescence of T cells and induces various age-related diseases, resulting in premature death. RIPK1 deficiency causes higher basal activation of mTORC1 (mechanistic target of rapamycin complex 1) that drives enhanced cytokine production, induction of senescence-related genes, and increased activation of caspase-3/7, which are restored by inhibition of mTORC1. Critically, normal aged T cells exhibit similar phenotypes and responses. Mechanistically, a combined deficiency of RIPK3 and caspase-8 inhibition restores the impaired proliferative responses; the elevated activation of Akt, mTORC1, extracellular signal-regulated kinase, and caspase-3/7; and the increased expression of senescence-related genes in RIPK1-deficient CD4 T cells. Last, we revealed that the senescent phenotype of RIPK1-deficient and aged CD4 T cells is restored in the normal tissue environment. Thus, we have clarified the function of RIPK3 and caspase-8 in inducing CD4 T cell senescence, which is modulated by environmental signals. |
