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A bioactive mammalian disaccharide associated with autoimmunity activates a STING-TBK1-dependent immune response

ABSTRACT: DNase III, also known as TREX1, is a 314 amino acid endoplasmic reticulum (ER) tail-anchored 3’ exonuclease where the N-terminal region contains the DNase domain and the C-terminal end controls TREX1 localization to the surface of the ER. Disease mutations in the C-terminal region alters TREX1 ability to interact with the oligosaccharyltransferase (OST) subunits Ribophorin 1 (RPN1) and DDOST leading to rapid hydrolysis of lipid-linked oligosaccharides (LLOs) into bioactive free oligosaccharides (fOS) in a switch-like manner. Bioassay-guided fractionation of the fOS pool revealed that the structure responsible for the bioactivity is a mannose (Man) b1-4 N-acetylglucosamine (GlcNAc) disaccharide. The bioactive disaccharide is produced from OST’s hydrolyzed LLOs in the cytoplasm and activates a STING-TBK1 dependent immune signal that leads to the upregulation of interferon-stimulated genes (ISGs) and chemokine genes.

ORGANISM(S): Mus musculus

PROVIDER: GSE129677 | GEO | 2019/04/16

REPOSITORIES: GEO

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