Conclusions
Plasma-derived, DNA containing-EVs induced STING-mediated proinflammatory effects in DM. Targeting the STING pathway may be a potential therapeutic approach for DM.
Methods
We collected and characterized EVs from plasma of healthy controls (HC) and DM patients; analyzed their abilities to trigger proinflammatory cytokines release by ELISA, and explored STING signaling pathway activation using immunoblot and immunofluorescent staining. STING signaling pathway inhibitors and RNAi were used to further investigate whether STING was involved in EVs-triggered proinflammatory response. DNase/lipid destabilizing agent was utilized to digest EVs and their captured DNA contents to evaluate how EVs triggered STING-mediated proinflammatory response in DM.
Results
EVs isolated from DM plasma triggered proinflammatory cytokines including type I IFN release with STING signaling pathway activation. The activated STING pathway was preferentially mediated by dsDNA captured by EVs. Suppression of STING or its downstream signaling proteins attenuated the EVs-mediated proinflammatory response. Conclusions: Plasma-derived, DNA containing-EVs induced STING-mediated proinflammatory effects in DM. Targeting the STING pathway may be a potential therapeutic approach for DM.