IKKβ对于保护T细胞免受肿瘤坏死因子α诱导的细胞凋亡至关重要。

IKKbeta is essential for protecting T cells from TNFalpha-induced apoptosis.

作者信息

Senftleben U, Li Z W, Baud V, Karin M

机构信息

Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California-San Diego, La Jolla, CA 92093, USA.

出版信息

Immunity. 2001 Mar;14(3):217-30. doi: 10.1016/s1074-7613(01)00104-2.

DOI:10.1016/s1074-7613(01)00104-2

PMID:11290332

Abstract

Transcription factor NF-kappaB, whose activation depends on the IKKbeta catalytic subunit of the IkappaB kinase, was assigned with both anti- and proapoptotic functions in T lymphocytes. To critically evaluate these functions, we transferred Ikkbeta-/- or wild-type (wt) fetal liver (FL) stem cells into lethally irradiated mice. Ikkbeta-/- radiation chimeras show thymic rudiments, aberrant lymphoid organs, and absence of T cells. T lymphopoiesis is rescued when Ikkbeta-/- stem cells are cotransferred with wt bone marrow, suggesting that IKKbeta may mediate its lymphopoietic function via extrinsic factors. However, almost normal development of Ikkbeta-/- T cells is observed upon removal of type 1 TNFalpha receptor, indicating that TNFalpha signaling accounts for the absence of Ikkbeta-/- T cells. Indeed, Ikkbeta-/- radiation chimeras exibit elevated circulating TNFalpha, and Ikkbeta-/- thymocytes display increased TNFalpha sensitivity.

摘要

转录因子NF-κB的激活依赖于IκB激酶的IKKβ催化亚基，它在T淋巴细胞中具有抗凋亡和促凋亡功能。为了严格评估这些功能，我们将IKKβ基因敲除或野生型（wt）胎肝（FL）干细胞移植到经致死剂量照射的小鼠体内。IKKβ基因敲除的辐射嵌合体表现出胸腺原基、异常淋巴器官以及T细胞缺失。当IKKβ基因敲除的干细胞与野生型骨髓共同移植时，T淋巴细胞生成得以挽救，这表明IKKβ可能通过外在因子介导其淋巴细胞生成功能。然而，在去除1型TNFα受体后，观察到IKKβ基因敲除的T细胞发育几乎正常，这表明TNFα信号传导是IKKβ基因敲除的T细胞缺失的原因。实际上，IKKβ基因敲除的辐射嵌合体循环TNFα水平升高，并且IKKβ基因敲除的胸腺细胞对TNFα的敏感性增加。