Figure 7.
Summary: Schematic of the innate anti-glioma immune circuit mediated by miR-1983-TLR7-NK axis. We discovered the existence of a TLR7-dependent anti-glioma NK-mediated innate immune circuit which is regulated by exosomal miR-1983 and is under the regulation of Gal-1. Right panel shows that GL26-GAL1KD glioma cells release miRNAs within the exosomes that can act as endogenous TLR7 ligands and bind to TLR7 through a UGUUU motif in miR-1983, in a myeloid cell population, such as cDCs and pDCs. TLR7 activation and downstream signaling through MyD88 activates IRF5 and IRF7 which in turn increase release of IFNβ. The release of IFNβ stimulates NK cells to kill glioma cells by releasing the Perforin and Granzyme B. Left panel shows that galectin-1 expressing GL26-GAL1WT glioma cells produces low level of miR-1983 which makes them unable to trigger the innate immune circuit. Altogether, we found the existence of a novel miR1983-TLR7-IFNβ-NK axis which triggers an anti-glioma NK-mediated innate immune circuit in GL26-GAL1KD glioma cells