An immunomodulatory GpG oligonucleotide for the treatment of autoimmunity via the innate and adaptive immune systems.
Bacterial DNA and immunostimulatory CpG oligodeoxynucleotides (ODNs) activate the innate immune system to produce proinflammatory cytokines. Shown to be potent Th1-like adjuvants, stimulatory CpG motifs are currently used as effective therapeutic vaccines for various animal models of infectious diseases, tumors, allergies, and autoimmune diseases. In this study, we show that the application of an immunomodulatory GpG ODN, with a single base switch from CpG to GpG, can effectively inhibit the activation of Th1 T cells associated with autoimmune disease. Moreover, this immunomodulatory GpG ODN suppresses the severity of experimental autoimmune encephalomyelitis in mice, a prototypic Th1-mediated animal disease model for multiple sclerosis.
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Beckman Center for Molecular Medicine, Stanford, CA 94305-5316, USA. peggy.ho@stanford.edu
Peggy P
PP
Ho
Paulo
P
Fontoura
Pedro J
PJ
Ruiz
Lawrence
L
Steinman
Hideki
H
Garren
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D018949:Antigens, CD1 / Q000096:biosynthesis; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology*; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015226:Dinucleoside Phosphates / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D015536:Down-Regulation / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000517:prevention & control; D005260:Female; D020862:GC Rich Sequence / Q000235:genetics / Q000276:immunology*; D006023:Glycoproteins / Q000096:biosynthesis; D006131:Growth Inhibitors / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D020672:I-kappa B Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D007113:Immunity, Innate / Q000235:genetics; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D018991:Myelin Proteolipid Protein / Q000037:antagonists & inhibitors / Q000502:physiology; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D010766:Phosphorylation; D012694:Serine / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
D000276:Adjuvants, Immunologic; D018949:Antigens, CD1; C437944:CD1C protein, human; D016207:Cytokines; D015226:Dinucleoside Phosphates; D006023:Glycoproteins; C480899:GpG-oligonucleotide; D006131:Growth Inhibitors; D000949:Histocompatibility Antigens Class II; D020672:I-kappa B Proteins; D007166:Immunosuppressive Agents; D004676:Myelin Basic Protein; D018991:Myelin Proteolipid Protein; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments; C405723:myelin basic protein Ac1-11(4Y); C435023:myelin proteolipid protein (139-151); D000072000:NF-KappaB Inhibitor alpha; C018309:guanylyl-(3'-5')-guanosine; D012694:Serine