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.

NF-κB（核因子κB）信号传导被认为对单阳性（SP）胸腺细胞发育至关重要，因为NF-κB上游激活因子（如IKK复合物）的丢失会阻止其发育。我们发现典型的NF-κB转录所需的RelA，cRel和p50的复合消融对胸腺细胞的发育没有影响。IKK缺乏的胸腺细胞对肿瘤坏死因子（TNF）诱导的细胞死亡具有敏锐的敏感性，而Rel缺乏的细胞仍然具有抵抗力，这使NF-κB作为胸腺细胞存活所需的IKK靶标的重要性产生了疑问。相反，我们发现IKK通过抑制丝氨酸/苏氨酸激酶RIPK1的细胞死亡诱导活性来控制胸腺细胞的存活。体内。最后，我们表明，IKK是保护Rel缺失的胸腺细胞免受RIPK1依赖性细胞死亡的必要条件，强调了胸腺发育过程中IKK的NF-κB依赖性功能。