Autoimmunity Gene IRGM Suppresses cGAS-STING and RIG-I-MAVS Signaling to control Interferon Response

ABSTRACT: Activation of the type 1 interferon response is extensively connected to the pathogenesis of autoimmune diseases. Loss of function of IRGM (Immunity Related GTPase M) has also been connected to several autoimmune diseases, but its mechanism of action is unknown. Here, we found that IRGM is a master negative regulator of the interferon response. Several nucleic acid sensing pathways leading to interferon-stimulated gene expression are highly activated in IRGM knockout mice and human cells. Mechanistically, we show that IRGM interacts with nucleic acid sensor proteins, including cGAS and RIG-I, and mediates their p62-dependent autophagic degradation to restrain interferon signaling. Further, IRGM deficiency results in defective mitophagy leading to the accumulation of defunct leaky mitochond

SUBMITTER: Dr. Santosh Chauhan 

PROVIDER: S-SCDT-EMBOR-2020-50051V1 | biostudies-other |

REPOSITORIES: biostudies-other