The role of the homeoboxprotein HoxA9 for plasmacytoid dendritic cell development and Toll-like receptor mediated FIN-alpha production

同源框蛋白 HoxA9 在浆细胞样树突状细胞发育和 Toll 样受体介导的 FIN-α 产生中的作用

• 批准号: 115837708
• 负责人: Professor Dr. Stefan Bauer
• 金额: --
• 依托单位: Institut für Immunologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/115837708?language=en
• 关键词: role; homeoboxprotein; HoxA9; plasmacytoid; dendritic

Dendritic cells play a major role in innate immunity by recognizing pathogens via Toll-like receptors (TLR). Especially plasmacytoid dendritic cells (pDCs) utilize TLR7 and TLR9 to sense viral nucleic acids and respond with strong IFN-α production. However, the molecular mechanisms of pDC development and their activity are not fully understood. By gene expression studies we have identified the homeobox protein HoxA9 as a differentially expressed protein in Flt3 ligand (Flt3L)-induced DCs when compared to other TLR9-responsive immune cells. HoxA9 is a transcription factor involved in myeloid, erythroid and lymphoid hematopoiesis as well as endothelial cell migration and angiogenesis. Our data indicate that HoxA9 deficiency regulates TLR9 mediated IFN-α production and pDC development. The aim of this project is to understand the role of HoxA9 for TLR-driven IFN-α production and the development of pDCs. Deciphering its function in pDCs will help to understand dendritic cell activity and this knowledge may be further exploited for enhancement of pDC-mediated immune responses against viral infections.

树突状细胞通过Toll样受体（TLR）识别病原体，在先天免疫中起主要作用。特别是浆细胞样树突状细胞（pDC）利用TLR 7和TLR 9来感测病毒核酸并以强IFN-α产生应答。然而，pDC发育的分子机制及其活性尚未完全了解。通过基因表达研究，我们已经确定同源框蛋白HoxA 9作为Flt 3配体（Flt 3L）诱导的DC中的差异表达蛋白，当与其他TLR 9应答免疫细胞相比。HoxA 9是参与骨髓、红细胞和淋巴造血以及内皮细胞迁移和血管生成的转录因子。我们的数据表明，HoxA 9缺陷调节TLR 9介导的IFN-α产生和pDC发育。本项目的目的是了解HoxA 9在TLR驱动的IFN-α产生和pDC开发中的作用。破译其在pDC中的功能将有助于理解树突状细胞的活性，并且这一知识可以进一步用于增强pDC介导的针对病毒感染的免疫应答。