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Survival of single positive thymocytes depends upon developmental control of RIPK1 kinase signaling by the IKK complex independent of NF-κB

Journal Contribution - Journal Article

Subtitle:Survival of single positive thymocytes depends upon developmental control of RIPK1 kinase signaling by the IKK complex independent of NF-kappa B
NF-kappa B(nuclear factor kappa B) signaling is considered critical for single positive (SP) thymocyte development because loss of upstream activators of NF-kappa B, such as the IKK complex, arrests their development. We found that the compound ablation of RelA, cRel, and p50, required for canonical NF-kappa B 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-kappa B 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-kappa B-independent function of IKK during thymic development.
Journal: IMMUNITY
ISSN: 1097-4180
Issue: 2
Volume: 50
Pages: 348 - 361
Publication year:2019
BOF-keylabel:yes
IOF-keylabel:yes
BOF-publication weight:10
CSS-citation score:2
Authors:International
Authors from:Government
Accessibility:Closed