Inhibition of a C-rich oligodeoxynucleotide on activation of immune cells in vitro and enhancement of antibody response in mice.

Immunology
Guang YangYongli Yu

Abstract

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.

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Citations

Jul 7, 2011·International Journal of Molecular Sciences·Zhiyuan FengXinhua Sun
Sep 4, 2012·International Journal of Molecular Sciences·Xu HouXinhua Sun
Jun 6, 2012·International Immunopharmacology·Yong-Sheng ZhangLi-Ying Wang
Oct 10, 2012·Antiviral Research·Nicolas BoivinGuy Boivin

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