ArfGAP2 deficiency ameliorates autoinflammation by regulating STING signaling and proton channel activity

The cGAS-STING pathway is a critical regulator of innate immunity.When cyclic GMP-AMP synthase (cGAS) detects aberrant cytosolic DNA, it synthesizes the second messenger 2'3'-cGAMP, which binds and activates stimulator of interferon genes (STING) on the endoplasmic reticulum (ER).Activated STING then translocates to the Golgi apparatus, where it recruits and mutually phosphorylates TANK-binding kinase 1 (TBK1) and interferon regulatory factor 3 (IRF3).Phosphorylated IRF3 dimerizes and translocates to the nucleus, where it drives the production of type 1 interferons (IFN-1).In addition to being activated by IFN-1, STING also engages the