Degree of STING activation is associated with disease outcomes

We read with interest the recent paper by Zhao et al ,1 which reported that stimulator of interferon genes (STING) signalling alleviated chronic pancreatitis (CP)-induced inflammation and fibrosis. There is increasing evidence that STING activation could lead to inflammatory response and fibrosis. In our opinion, this contention is associated with three major issues: the form of stimulators that activate STING, the degree of STING activation and the type of immune cell lineages activated STING signalling are able to affect its role in the process of disease. Self-DNA released from various types of cells during infection or inflammation may stimulate cyclic guanosine monophosphate–adenosine monophosphate (GMP–AMP)  synthase (cGAS)–STING pathway to different degrees. Zhao et al 1 did not investigate how STING signalling was activated; however, the amount, manner and rate of DNA release under different ways of cell deaths all played important roles in activating downstream pathways. Additionally, recent reports indicated that the extent of DNA oxidation is a key factor in promoting an enhanced inflammatory …