| First Author | Webb LV | Year | 2019 |
| Journal | Immunity | Volume | 50 |
| Issue | 2 | Pages | 348-361.e4 |
| PubMed ID | 30737145 | Mgi Jnum | J:282495 |
| Mgi Id | MGI:6381053 | Doi | 10.1016/j.immuni.2019.01.004 |
| Citation | Webb LV, et al. (2019) Survival of Single Positive Thymocytes Depends upon Developmental Control of RIPK1 Kinase Signaling by the IKK Complex Independent of NF-kappaB. Immunity 50(2):348-361.e4 |
| abstractText | NF-kappaB (nuclear factor kappaB) signaling is considered critical for single positive (SP) thymocyte development because loss of upstream activators of NF-kappaB, such as the IKK complex, arrests their development. We found that the compound ablation of RelA, cRel, and p50, required for canonical NF-kappaB transcription, had no impact upon thymocyte development. While IKK-deficient thymocytes were acutely sensitive to tumor necrosis factor (TNF)-induced cell death, Rel-deficient cells remained resistant, calling into question the importance of NF-kappaB as the IKK target required for thymocyte survival. Instead, we found that IKK controlled thymocyte survival by repressing cell-death-inducing activity of the serine/threonine kinase RIPK1. We observed that RIPK1 expression was induced during development of SP thymocytes and that IKK was required to prevent RIPK1-kinase-dependent death of SPs in vivo. Finally, we showed that IKK was required to protect Rel-deficient thymocytes from RIPK1-dependent cell death, underscoring the NF-kappaB-independent function of IKK during thymic development. |
