The TLR7/8 ligand resiquimod targets monocyte-derived dendritic cell differentiation via TLR8 and augments functional dendritic cell generation
| Autor: | Thomas Kubin, Marion Jurk, Holger Hackstein, Angela Knoche, Gregor Bein, Jochen Poeling, Jörg Vollmer, Angelika Nockher |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
CD14
Immunology Interleukin-3 Receptor alpha Subunit Dendritic cell differentiation In Vitro Techniques Ligands Transfection Monocytes Oligodeoxyribonucleotides Antisense chemistry.chemical_compound Humans Receptor Cell Proliferation HLA-D Antigens MHC class II Base Sequence Guanosine biology Imidazoles virus diseases Cell Differentiation Dendritic Cells T-Lymphocytes Helper-Inducer Dendritic cell TLR7 TLR8 Cell biology HEK293 Cells Toll-Like Receptor 7 chemistry Toll-Like Receptor 8 Toll-Like Receptor 9 Aminoquinolines biology.protein Resiquimod |
| Zdroj: | Cellular Immunology. 271:401-412 |
| ISSN: | 0008-8749 |
| DOI: | 10.1016/j.cellimm.2011.08.008 |
| Popis: | Imidazoquinolone compounds, such as resiquimod are Toll-like receptor (TLR) 7/8 ligands representing novel immune response modifiers undergoing clinical testing. Resiquimod has been reported to modulate conventional human monocyte-derived DC (moDC) differentiation, but the role of TLR7 and TLR8 is unclear. We directly dissected the TLR7- and TLR8-dependency by employing selective TLR7 ligands and resiquimod-coculture experiments with inhibitory oligonucleotides (iODN) suppressing TLR7, TLR7+8 or TLR7+8+9. Selective TLR7 ligands did not affect conventional moDC differentiation as analyzed by CD14/CD1a expression. iODN experiments confirmed that resiquimod's effects during DC differentiation were antagonized only with TLR8 iODNs. Direct comparison of resiquimod DC with TLR7- and control-DC revealed significantly higher T-cell costimulatory molecule and MHC class II expression. Resiquimod DC promoted significantly stronger allogeneic T-cell proliferation and stronger naïve CD4(+) T-cell proliferation. These results indicate the relevance of TLR8 for human monocyte-derived DC differentiation and maturation and may be relevant for clinical trials employing resiquimod. |
| Databáze: | OpenAIRE |
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