A GpC-Rich Oligonucleotide Acts on Plasmacytoid Dendritic Cells To Promote Immune Suppression

作者：Volpi Claudia; Fallarino Francesca; Bianchi Roberta; Orabona Ciriana; De Luca Antonella; Vacca Carmine; Romani Luigina; Gran Bruno; Grohmann Ursula; Puccetti Paolo; Belladonna Maria L^*

来源：The Journal of Immunology, 2012, 189(5): 2283-2289.

DOI：10.4049/jimmunol.1200497

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-kappa B 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. The Journal of Immunology, 2012, 189: 2283-2289.

• 出版日期2012-9-1