A human microsatellite DNA-mimicking oligodeoxynucleotide with CCT repeats negatively regulates TLR7/9-mediated innate immune responses via selected TLR pathways.
A human microsatellite DNA-mimicking ODN (MS ODN) composed of CCT repeats, designated as SAT05f, has been studied for its capacity of negatively regulating innate immunity induced by TLR7/TLR9 agonists in vitro and in mice. The result showed that SAT05f could down-regulate TLR7/9-dependent IFN-alpha production in cultured human PBMC stimulated by inactivated Flu virus PR8 or HSV-1 or CpG ODN or imiquimod, protect d-GalN-treated mice from lethal shock induced by TLR9 agonist, not by TLR3/4 agonist. In addition, SAT05f significantly inhibit IFN-alpha production from purified human plasmacytoid cells (pDCs) stimulated by CpG ODN. Interestingly, SAT05f could up-regulate CD80, CD86, and HLA-DR on the pDCs in vitro, implying that SAT05f-mediated inhibition on IFN-alpha production could be related to the activation of pDCs. The data suggest that SAT05f could be developed as a candidate medicament for the treatment of TLR7/9 activation-associated diseases by inhibiting TLR7/9 signaling pathways.
Sun
Ran
R
Department of Immunology, Jilin University, Changchun, China.
Sun
Luguo
L
Bao
Musheng
M
Zhang
Yongsheng
Y
Wang
Li
L
Wu
Xiuli
X
Hu
Dali
D
Liu
Yongjun
Y
Yu
Yongli
Y
Wang
Liying
L
D000818:Animals; D002522:Chlorocebus aethiops; D004266:DNA Virus Infections / Q000276:immunology / Q000821:virology; D003713:Dendritic Cells / Q000276:immunology; D004285:Dogs; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D016898:Interferon-alpha / Q000096:biosynthesis / Q000276:immunology; D053208:Kaplan-Meier Estimate; D008562:Membrane Glycoproteins / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018895:Microsatellite Repeats / Q000276:immunology*; D009838:Oligodeoxyribonucleotides / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D012327:RNA Virus Infections / Q000276:immunology / Q000821:virology; D011897:Random Allocation; D013047:Specific Pathogen-Free Organisms; D051199:Toll-Like Receptor 7 / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000276:immunology; D014709:Vero Cells
D016898:Interferon-alpha; D008562:Membrane Glycoproteins; D009838:Oligodeoxyribonucleotides; C477038:Tlr7 protein, mouse; C495370:Tlr9 protein, mouse; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9