The TLR7/8 ligand resiquimod targets monocyte-derived dendritic cell differentiation via TLR8 and augments functional dendritic cell generation

作者：Hackstein Holger^*; Knoche Angela; Nockher Angelika; Poeling Jochen; Kubin Thomas; Jurk Marion; Vollmer Joerg; Bein Gregor

来源：Cellular Immunology, 2011, 271(2): 401-412.

DOI：10.1016/j.cellimm.2011.08.008

• Adjuvant
• Immune modulation

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 naive 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.

• 出版日期2011