Kruse M, Rosorius O, Krätzer F, Bevec D, Kuhnt C, Steinkasserer A, Schuler G, Hauber J
Department of Dermatology, University Erlangen-Nürnberg, D-91054 Erlangen, Germany.
J Exp Med. 2000 May 1;191(9):1581-90. doi: 10.1084/jem.191.9.1581.
Dendritic cells (DCs), nature's adjuvant, must mature to sensitize T cells. However, although the maturation process is essential, it is not yet fully understood at the molecular level. In this study, we investigated the course of expression of the unique hypusine-containing protein eukaryotic initiation factor 5A (eIF-5A), which is part of a particular RNA nuclear export pathway, during in vitro generation of human DCs. We show that eIF-5A expression is significantly upregulated during DC maturation. Furthermore, an inhibitor of the hypusine modification, GC7 (N(1)-guanyl-1, 7-diaminoheptane), prevents CD83 surface expression by apparently interfering with nucleocytoplasmic translocation of the CD83 mRNA and, importantly, significantly inhibits DC-mediated T lymphocyte activation. The data presented suggest that CD83 mRNA is transported from the nucleus to the cytoplasm via a specific nuclear export pathway and that hypusine formation appears to be essential for the maturation of functional DCs. Therefore, pharmacological interference with hypusine formation may provide a new possibility to modulate DC function.
树突状细胞（DCs），即天然佐剂，必须成熟才能使T细胞致敏。然而，尽管成熟过程至关重要，但在分子水平上尚未完全了解。在本研究中，我们调查了在人DCs的体外生成过程中，独特的含hypusine蛋白真核起始因子5A（eIF-5A）的表达过程，该蛋白是特定RNA核输出途径的一部分。我们发现，在DC成熟过程中，eIF-5A的表达显著上调。此外，hypusine修饰的抑制剂GC7（N(1)-鸟苷基-1,7-二氨基庚烷）通过明显干扰CD83 mRNA的核质转运来阻止CD83表面表达，并且重要的是，显著抑制DC介导的T淋巴细胞活化。所呈现的数据表明，CD83 mRNA通过特定的核输出途径从细胞核转运到细胞质，并且hypusine的形成似乎对于功能性DC的成熟至关重要。因此，对hypusine形成的药理学干扰可能为调节DC功能提供新的可能性。
