| First Author | Rueckert C | Year | 2017 |
| Journal | FASEB J | Volume | 31 |
| Issue | 7 | Pages | 3107-3115 |
| PubMed ID | 28396343 | Mgi Jnum | J:252810 |
| Mgi Id | MGI:5926812 | Doi | 10.1096/fj.201601093R |
| Citation | Rueckert C, et al. (2017) Cyclic dinucleotides modulate induced type I IFN responses in innate immune cells by degradation of STING. FASEB J 31(7):3107-3115 |
| abstractText | The cyclic dinucleotides, GMP-AMP (cGAMP) and c-di-AMP [bis-(3',5')-cyclic dimeric AMP], are potent type I IFN inducers via STING-TBK1-IRF3 cascade. They are promising adjuvants that promote antigen-specific humoral and cellular immune responses in different preclinical models; however, an optimal outcome of vaccination depends on a balanced immune activation. Here, we characterize the process of IFN-beta induction by c-di-AMP and cGAMP in an in vitro model on the basis of primary mouse dendritic cells. Results obtained show decreased IFN-beta production upon prolonged cell stimulation. We demonstrate that this effect depends on c-di-AMP/cGAMP-mediated down-regulation of stimulator of IFN gene (STING) protein levels. These results were confirmed by using human peripheral blood mononuclear cell-derived dendritic cells. Studies performed to explore the potential mechanism of STING modulation suggested proteolytic degradation to be a contributing factor to the observed decrease in cellular STING levels. Our work contributes to the elucidation of the molecular mode of action of vaccine constituents, which, in turn, is a prerequisite for the rational design of vaccines with predictable efficacy and safety profiles-Rueckert, C., Rand, U., Roy, U., Kasmapour, B., Strowig, T., Guzman, C. A. Cyclic dinucleotides modulate induced type I IFN responses in innate immune cells by degradation of STING. |
