SMPDL3A links cholesterol metabolism to the cGAS-STING pathway

Liver X receptor (LXR), well known for its role in cholesterol metabolism, also has anti-inflammatory properties. In this issue of Immunity, Hou et al. demonstrate that LXR signaling induces SMPDL3A, a cGAMP-degrading enzyme that restricts cGAS-cGAMP-STING innate immune signaling, providing a mechanistic link between lipid metabolism and inflammation. Liver X receptor (LXR), well known for its role in cholesterol metabolism, also has anti-inflammatory properties. In this issue of Immunity, Hou et al. demonstrate that LXR signaling induces SMPDL3A, a cGAMP-degrading enzyme that restricts cGAS-cGAMP-STING innate immune signaling, providing a mechanistic link between lipid metabolism and inflammation. SMPDL3A is a cGAMP-degrading enzyme induced by LXR-mediated lipid metabolism to restrict cGAS-STING DNA sensingHou et al.ImmunityOctober 26, 2023In BriefThe mechanism of how LXR-mediated lipid metabolism is involved in anti-inflammatory effects is unclear. Hou et al. find that LXR agonists induce the expression of SMPDL3A to degrade cGAMP, thereby inhibiting cGAS-STING DNA-sensing pathway. Full-Text PDF