title: A GpC-rich oligonucleotide acts on plasmacytoid dendritic cells to promote immune suppression.
abstract: 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-κB family members and TGF-β-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.
authors: Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia 06126, Italy.
authors: Claudia
authors: C
authors: Volpi
authors: Francesca
authors: F
authors: Fallarino
authors: Roberta
authors: R
authors: Bianchi
authors: Ciriana
authors: C
authors: Orabona
authors: Antonella
authors: A
authors: De Luca
authors: Carmine
authors: C
authors: Vacca
authors: Luigina
authors: L
authors: Romani
authors: Bruno
authors: B
authors: Gran
authors: Ursula
authors: U
authors: Grohmann
authors: Paolo
authors: P
authors: Puccetti
authors: Maria L
authors: ML
authors: Belladonna
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects / Q000235:genetics*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000096:biosynthesis; D016899:Interferon-beta / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000235:genetics; D009838:Oligodeoxyribonucleotides / Q000235:genetics / Q000494:pharmacology*; D017434:Protein Structure, Tertiary; D017472:Receptors, Interleukin-1 / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology; D051199:Toll-Like Receptor 7 / Q000502:physiology; D014158:Transcription, Genetic / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000502:physiology
chemical_list: C423449:CpG ODN 1826; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D017472:Receptors, Interleukin-1; D051199:Toll-Like Receptor 7; D016212:Transforming Growth Factor beta; D016899:Interferon-beta