Dendritic cell development and survival require distinct NF-kappaB subunits.
Dendritic cell development and survival require distinct NF-kappaB subunits.
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DOI：
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发表时间：
2002
期刊：
影响因子：
32.4
通讯作者：
F. Ouaaz;J. Arron;Ye Zheng;Yongwon Choi;A. Beg
中科院分区：
文献类型：
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作者：
F. Ouaaz;J. Arron;Ye Zheng;Yongwon Choi;A. Beg
尽管树突状细胞(DC)在调节T淋巴细胞激活中的作用已被证实，但负责控制DC功能的细胞内机制在很大程度上尚不清楚。在这里，我们研究了免疫调节核因子-kappaB转录因子p50、relA和cRel亚单位缺陷小鼠的DC。尽管缺乏单个核因子-kappaB亚基的小鼠的DC发育和功能正常，但双缺陷p50(-/-)relA(-/-)DC的发育显著受损。相反，p50(-/-)cRel(-/-)小鼠的DC发育正常，但CD40L和TRANCE诱导的存活和IL-12的产生被取消。令人惊讶的是，尽管kappaB结合活性显著降低，但MHC和共刺激分子的表达没有明显的损害。因此，这些结果表明，核因子-kappaB蛋白在调节DC的发育、存活和细胞因子产生方面具有重要的亚基特异性功能。
Despite the established role of dendritic cells (DCs) in regulating T lymphocyte activation, intracellular mechanisms responsible for controlling DC function are largely undefined. Here, we have studied DCs from mice deficient in the p50, RelA, and cRel subunits of the immunomodulatory NF-kappaB transcription factor. Although DC development and function was normal in mice lacking individual NF-kappaB subunits, development of doubly deficient p50(-/-)RelA(-/-) DCs was significantly impaired. In contrast, DCs from p50(-/-)cRel(-/-) mice developed normally, but CD40L- and TRANCE-induced survival and IL-12 production was abolished. Surprisingly, no significant impairment in MHC and costimulatory molecule expression was seen, despite significantly reduced kappaB site binding activity. These results therefore indicate essential, subunit-specific functions for NF-kappaB proteins in regulating DC development, survival, and cytokine production.