IFI16 is Required for an Oligodeoxynucleotide with CCT Repeats to Induce Type I Interferon Production in U937 Cells
Journal Title: Biomedical Journal of Scientific & Technical Research (BJSTR) - Year 2018, Vol 19, Issue 4
Abstract
In previous study, we found that an oligodeoxynucleotide with CCT repeats (CCT ODN) could display immunosuppressive roles for TLR9 response in mice and in vitro. However, in this study, we found that CCT ODN could obviously elevate the mRNA levels of interferon-inducible protein 16 (IFI16) but no other DNA sensor such as AIM2, which belongs to same family of IFI16, in human monocyte line U937 cells when stimulated for 2 hours. At this condition, CCT ODN could also increase the level of interferon- (IFN-) mRNA in U937 cells. To confirm the CCT ODN-induced IFN- production associated with IFI16, we knocked down IFI16 expression and found that CCT ODN lost its induction role of IFN- production. Then, by using confocal microscope analysis, we found that IFI16 and CCT ODN could co-localize in the cytosol. The cytosol CCT ODN might be delivered by the cell surface DEC-205 that was down regulated after CCT ODN stimulation. Together, the study indicates that CCT ODN can activate IFI16 by associating with DEC-205 to mediate IFN- production in U937 cells, which may be the reason for explaining CCT ODN to attenuate the TLR9 response. The oligodeoxynucleotide with CCT repeats (CCT ODN) is a human microsatellite DNA sequence-based immunosuppressive ODN and displayed selectively negative regulatory role on TLR9 activation [1-3]. It can restrain TLR9 trafficking in immune cells, rescue mice from lethal shock sepsis induced by CpG ODN (TLR9 agonist) and decrease serum anti-DNA antibody levels in mice with lupus-like nephritis with unknown mechanism [4]. As an artificial synthesized single-stranded DNA (ssDNA), CCT ODN might display its role through certain DNA sensor. We know now, in addition to TLR9, there are several DNA sensors, such as DAI, RNA polymerase III, LRRFIP1, AIM2, IFI16 and others, which can sense intracellular DNA to initiate innate immune responses [5-8].
Authors and Affiliations
Shuang Gao, Hong Zhang,, He Li, Tianbo Li, Aobo Du, Xiaoxu Ling, Boqun Cheng, Zhimin Zhang
Keywords
Related Articles
- EP ID EP622664
- DOI 10.26717/BJSTR.2019.19.003357
- Views 135
- Downloads 0
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