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Inhibition of a C‐rich oligodeoxynucleotide on activation of immune cells in vitro and enhancement of antibody response in mice
Author(s) -
Yang Guang,
Wan Min,
Zhang Yongsheng,
Sun Luguo,
Sun Ran,
Hu Dali,
Zhou Xiaojing,
Wang Li,
Wu Xiuli,
Wang Liying,
Yu Yongli
Publication year - 2010
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2010.03322.x
Subject(s) - tlr9 , cpg oligodeoxynucleotide , immune system , biology , peripheral blood mononuclear cell , in vitro , toll like receptor 9 , cpg site , guanosine , antibody , immunostimulant , herpes simplex virus , tlr7 , microbiology and biotechnology , virus , immunology , toll like receptor , innate immune system , biochemistry , gene , gene expression , dna methylation
Summary 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 ATCT 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.