A human microsatellite DNA-mimicking oligodeoxynucleotide with CCT repeats negatively regulates TLR7/9-mediated innate immune responses via selected TLR pathways

作者：Sun, Ran; Sun, Luguo; Bao, Musheng; Zhang, Yongsheng; Wang, Li; Wu, Xiuli; Hu, Dali; Liu, Yongjun; Yu, Yongli^*; Wang, Liying

来源：Clinical Immunology, 2010, 134(3): 262-276.

DOI：10.1016/j.clim.2009.11.009

• MS ODN
• IFN-alpha
• TLR7/9 selective inhibition
• TLR activation-associated diseases
• pDC activation

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.

• 出版日期2010-3
• 单位吉林大学