| First Author | Volpi C | Year | 2012 |
| Journal | J Immunol | Volume | 189 |
| Issue | 5 | Pages | 2283-9 |
| PubMed ID | 22844124 | Mgi Jnum | J:189860 |
| Mgi Id | MGI:5447134 | Doi | 10.4049/jimmunol.1200497 |
| Citation | Volpi C, et al. (2012) A GpC-rich oligonucleotide acts on plasmacytoid dendritic cells to promote immune suppression. J Immunol 189(5):2283-9 |
| abstractText | Short synthetic oligodeoxynucleotides (ODNs) rich in CpG or GpG motifs have been considered as potential modulators of immunity in clinical settings. In this study, we show that a synthetic GpC-ODN conferred highly suppressive activity on mouse splenic plasmacytoid dendritic cells, demonstrable in vivo in a skin test assay. The underlying mechanism involved signaling by noncanonical NF-kappaB family members and TGF-beta-dependent expression of the immunoregulatory enzyme IDO. Unlike CpG-ODNs, the effects of GpC-ODN required TLR7/TRIF-mediated but not TLR9/MyD88-mediated events, as do sensing of viral ssRNA and the drug imiquimod. Induction of IDO by a GpC-containing ODN could also be demonstrated in human dendritic cells, allowing those cells to assist FOXP3+ T cell generation in vitro. Among potentially therapeutic ODNs, this study identifies GpC-rich sequences as novel activators of TLR7-mediated, IDO-dependent regulatory responses. |
