UNC93B1 curbs cytosolic DNA signaling by promoting STING degradation

Abstract UNC93B1 is a trafficking chaperone of endosomal Toll‐like receptors (TLRs) and plays an essential role in the TLR‐mediated innate signaling. However, whether it also involved other immune sensing or cellular pathways remains largely unexplored. Here we investigated cytosolic DNA‐triggered cGAS‐STING signaling mouse human cell lines. We showed that while deficiency blunts signal transduction by TLR3, augments responses to DNA stimulation virus infection. Mechanistic study reveals distinct action upon STING, but not parts along cGAS‐STING‐TBK1 axis, through regulating protein level STING at both resting DNA‐stimulated conditions. can directly interact traffic with disruption this interaction causes accumulation subsequently leads augmented its activation. These findings reveal new function negatively STING‐mediated responses.