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Title
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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
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Author
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Abstract
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| NF-κB (nuclear factor κB) signaling is considered critical for single positive (SP) thymocyte development because loss of upstream activators of NF-κB, such as the IKK complex, arrests their development. We found that the compound ablation of RelA, cRel, and p50, required for canonical NF-κB 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-κB 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-κB-independent function of IKK during thymic development. |
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Language
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English
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Source (journal)
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Immunity. - Cambridge, Mass.
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Publication
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Cambridge, Mass.
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2019
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ISSN
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1074-7613
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DOI
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10.1016/J.IMMUNI.2019.01.004
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Volume/pages
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50
:2
(2019)
, p. 348-361.e4
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ISI
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000459006700011
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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