Regulation of naive T cell function by the NF-κB2 pathway
Regulation of naive T cell function by the NF-κB2 pathway
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DOI：
10.1038/ni1351
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发表时间：
2006-07-01
影响因子：
30.5
通讯作者：
Sprent, Jonathan
中科院分区：
文献类型：
--
作者：
Ishimaru, Naozumi;Kishimoto, Hidehiro;Sprent, Jonathan
T 细胞激活涉及多个信号通路的协调，包括“经典”转录因子 NF-kappa B 成分 NF-kappa B1-RelA 的信号通路。 “非经典”NF-kappa B2-RelB 途径的功能尚不清楚，尽管缺乏该途径成分的 T 细胞存在激活缺陷。在这里，我们发现缺乏NF-κB诱导激酶的小鼠具有复杂的表型，包括由CD25-Foxp3记忆CD4(+)细胞介导的免疫抑制，以及在这些细胞不存在的情况下，高反应性幼稚CD4(+) T细胞，其在过继转移到缺乏重组激活基因的宿主后引起自身免疫损伤。生化研究表明，NF-kappa B2 (p100) 限制 NF-kappa B1-RelA 的核转位，从而发挥细胞内在机制的作用，从而充当初始 T 细胞激活的调节“刹车”。
T cell activation involves the orchestration of several signaling pathways, including that of the 'classical' transcription factor NF-kappa B components NF-kappa B1-RelA. The function of the 'nonclassical' NF-kappa B2-RelB pathway is less clear, although T cells lacking components of this pathway have activation defects. Here we show that mice deficient in NF-kappa B-inducing kinase have a complex phenotype consisting of immunosuppression mediated by CD25-Foxp3-memory CD4(+) cells and, in the absence of those cells, hyper-responsive naive CD4(+) T cells, which caused autoimmune lesions after adoptive transfer into hosts deficient in recombination-activating genes. Biochemical studies indicated involvement of a cell-intrinsic mechanism in which NF-kappa B2 (p100) limits nuclear translocation of NF-kappa B1-RelA and thereby functions as a regulatory 'brake' for the activation of naive T cells.