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

• Applicant: Professor Dr. Stefan Bauer
• Subject Area: Immunology
• Term: from 2009 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 115837708

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.

• DFG Programme: Research Grants