The aim of the VIB researchers is not only to block TNFR1, but they also want to gain a better understanding of how it is regulated. In other words, which mechanisms cause a decrease in TNFR1 expression. This could also be used in a therapeutic setting.
The group of Claude Libert discovered that a particular mouse strain, called SPRET/Ei, exhibits barely any response to TNF. Extensive research revealed that this is the result of very low expression of TNFR1 in these mice, which in turn is caused by the elevated expression of a micro-RNA molecule called miR-511.
Claude Libert: “Injection of this miR-511 did indeed cause a decrease in TNFR1 in these mice and made the mice resistant to TNF. Further research will have to be performed in the future to determine whether such miR injections can have a therapeutic use.
Glucocorticoids, steroids that are often prescribed to combat inflammation, were found to increase the expression of miR-511. Therefore, the effect of glucocorticoids is probably partly attributable to the fact that they cause a decrease in the concentration of TNFR1 via this molecular mechanism, resulting in a decreased response to TNF.