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- W2981830386 abstract "Abstract Activation of type 1 interferon response is extensively connected with the antiviral immunity and pathogenesis of autoimmune diseases. Here, we found that IRGM, whose deficiency is linked with the genesis of several autoimmune disorders, is a master negative regulator of the interferon response. Mechanistically, we show that IRGM interacts with nucleic acid sensor proteins, including cGAS and RIG-I, and mediates their autophagic degradation to restrain activation of interferon signaling. Further, IRGM maintains mitophagy flux, and its deficiency results in the accumulation of defunct leaky mitochondria that releases cytosolic DAMPs triggering activation of interferon responses via cGAS-STING and RIG-I-MAVS signaling axis. Due to an enduring type 1 IFN response in IRGM-deficient cells and mice, they were intrinsically resistant to infection of the Japanese Encephalitis virus, Herpes Simplex virus, and Chikungunya virus. Altogether, this study defines the molecular mechanisms by which IRGM maintains interferon homeostasis and protects from autoimmune diseases. Further, it identifies IRGM as a broad therapeutic target for defense against viruses. Graphical Abstract" @default.
- W2981830386 created "2019-11-01" @default.
- W2981830386 creator A5001285400 @default.
- W2981830386 creator A5009087678 @default.
- W2981830386 creator A5014193753 @default.
- W2981830386 creator A5021379933 @default.
- W2981830386 creator A5025398045 @default.
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- W2981830386 creator A5041019601 @default.
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- W2981830386 creator A5061095063 @default.
- W2981830386 creator A5061904937 @default.
- W2981830386 creator A5062738658 @default.
- W2981830386 creator A5077810105 @default.
- W2981830386 date "2019-10-22" @default.
- W2981830386 modified "2023-09-26" @default.
- W2981830386 title "Autoimmunity Risk Gene IRGM is a Master Negative Regulator of Interferon Response by Controlling the Activation of cGAS-STING and RIG-I-MAVS Signaling Pathways" @default.
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