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 Immunity Related GTPase M (IRGM) has also been associated 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 mitochon

SUBMITTER: Jena KK 

PROVIDER: S-EPMC7507369 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature