Transforming growth factor β1 up-regulates interferon regulatory factor 8 during dendritic cell development

被引：16
作者：
Ju, Xin-Sheng [1 ]
Ruau, David [1 ]
Jantti, Piritta [1 ]
Sere, Kristin [1 ]
Becker, Christiane [1 ]
Wiercinska, Eliza [1 ]
Bartz, Clemens [1 ]
Erdmann, Bettina [1 ]
Dooley, Steven [1 ]
Zenke, Martin [1 ]
机构：
[1] Aachen Univ Hosp, RWTH, Dept Cell Biol, Inst Biomed Engn, D-52074 Aachen, Germany
来源：
EUROPEAN JOURNAL OF IMMUNOLOGY | 2007年 / 37卷 / 05期
关键词：
dendritic cells; IFN consensus sequence binding protein; IRF-8; TGF-beta; 1; transforming growth factor;
D O I：
10.1002/eji.200636504
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
Langerhans cells (LC) represent the cutaneous contingent of dendritic cells (DC). Their development critically depends on transforming growth factor beta 1 (TGF-beta 1) as demonstrated by analysis of TGF-beta 1(-1-) mice, which lack LC. Here we used a two-step culture system and transcriptional profiling by DNA microarrays to search for TGF-beta 1 target genes in DC. The study identified interferon regulatory factor 8 (IRF-8) as a novel target gene of TGF-beta 1 signaling in DC. TGF-beta 1 effectively induced Smad2/3 phosphorylation and IRF-8 RNA and protein expression. Blocking the TGF-beta 1/Smad pathway by ectopic expression of inhibitory Smad7 and by SB431542 inhibitor abolished TGF-beta 1 induced up-regulation of IRF-8. Furthermore, TGF-beta 1-dependent induction of IRF-8 occurred in the absence of protein biosynthesis, suggesting a direct action of TGF-beta 1/Smad signaling on IRF-8 gene activity. TGF-beta 1 also induced expression of the chemokine receptor CCR7 and enhanced DC migration towards CCR7 ligand ELC. DC of IRF-8(-/-) mice show reduced CCR7 expression and migratory activity, thereby implicating the TGF-beta 1/Smad/IRF-8 signaling pathway in CCR7 regulation. Thus, this study identified a novel TGF-beta 1/Smad/IRF-8 signaling pathway with an impact on DC phenotype and function.
引用
收藏
页码：1174 / 1183
页数：10
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