Inhibition of a C-rich oligodeoxynucleotide on activation of immune cells in vitro and enhancement of antibody response in mice.
To explore the possibility that human mitochondrial genomic DNA-mimicking oligodeoxynucleotides could regulate the immune response, a series of mitochondrial DNA-based oligodeoxynucleotides (MTODNs) were designed and studied to determine their immunoregulatory effects on immune cells activated by toll-like receptor (TLR) stimulation. The results showed that a C-rich MTODN, designated MT01, was able to inhibit the proliferation of human peripheral blood mononuclear cells (PBMCs) induced by cytosine-phosphate-guanosine (CpG) oligodeoxynucleotides (ODNs) and the production of type I interferon (IFN) from human PBMCs stimulated by TLR agonists, including inactivated influenza virus, imiquimod, inactivated herpes simplex virus-1 (HSV-1) and CpG ODNs. In addition, MT01 inhibited the CpG ODN-enhanced antibody response and this inhibition could be related to the antagonism of TLR9-activation pathways in B cells. Notably, unlike the G-rich suppressive ODNs reported, MT01 is composed of ACCCCCTCT repeats. These data imply that MT01 represents a novel class of immunosuppressive ODNs that could be candidate biologicals with therapeutic use in TLR activation-associated diseases.
Yang
Guang
G
Department of Molecular Biology, Medical College of Norman Bethune, Jilin University, Changchun, China.
Wan
Min
M
Zhang
Yongsheng
Y
Sun
Luguo
L
Sun
Ran
R
Hu
Dali
D
Zhou
Xiaojing
X
Wang
Li
L
Wu
Xiuli
X
Wang
Liying
L
Yu
Yongli
Y
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects* / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects*; D002522:Chlorocebus aethiops; D004272:DNA, Mitochondrial / Q000494:pharmacology*; D005260:Female; D018259:Herpesvirus 1, Human / Q000276:immunology; D006801:Humans; D000077271:Imiquimod; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007370:Interferon Type I / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D009975:Orthomyxoviridae / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000819:agonists / Q000276:immunology; D014709:Vero Cells
D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; C408982:CPG-oligonucleotide; D004272:DNA, Mitochondrial; D007166:Immunosuppressive Agents; D007370:Interferon Type I; C000600078:ODN MT01; D009838:Oligodeoxyribonucleotides; C495371:TLR9 protein, human; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D000077271:Imiquimod