ArticleNature communications2019
A bioactive mammalian disaccharide associated with autoimmunity activates STING-TBK1-dependent immune response.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 25 citations in OpenAlex.
- Reverse thiophosphorylase activity of a glycoside phosphorylase in the synthesis of an unnatural Manβ1,4GlcNAc library.Chemical science · 2023Article
- Stereoselective synthesis of photoactivatable Man(β1,4)GlcNAc-based bioorthogonal probes.Tetrahedron letters · 2023Article
- TREX1 cytosolic DNA degradation correlates with autoimmune disease and cancer immunity.Clinical and experimental immunology · 2023Article
- Multifaceted functions of STING in human health and disease: from molecular mechanism to targeted strategy.Signal transduction and targeted therapy · 2022Review
- Article
- Chemoproteomic mapping of human milk oligosaccharide (HMO) interactions in cells.RSC chemical biology · 2022Article
- Organellar homeostasis and innate immune sensing.Nature reviews. Immunology · 2022Review
- Impact of Multiple Sclerosis Risk Polymorphism rs7665090 on MANBA Activity, Lysosomal Endocytosis, and Lymphocyte Activation.International journal of molecular sciences · 2022Article
- Dexmedetomidine and Ketamine Attenuated Neuropathic Pain Related BehaviorsFrontiers in synaptic neuroscience · 2022Article
- ER-directed TREX1 limits cGAS activation at micronuclei.Molecular cell · 2021Article
- MDA5 Is an Essential Sensor of a Pathogen-Associated Molecular Pattern Associated with Vitality That Is Necessary for Host Resistance againstJournal of immunology (Baltimore, Md. : 1950) · 2020Article
- TREX1 - Apex predator of cytosolic DNA metabolism.DNA repair · 2020Article
- The cGAS-STING Pathway in Hematopoiesis and Its Physiopathological Significance.Frontiers in immunology · 2020Review
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Glycans from microbial pathogens are well known pathogen-associated molecular patterns that are recognized by the host immunity; however, little is known about whether and how mammalian self-glycans activate the host immune response, especially in the context of autoimmune disease. Using biochemical fractionation and two-dimensional HPLC, we identify an abundant and bioactive free glycan, the Manβ1-4GlcNAc disaccharide in TREX1-associated autoimmune diseases. We report that both monosaccharide residues and the β1-4 linkage are critical for bioactivity of this disaccharide. We also show that Manβ1-4GlcNAc is produced by oligosaccharyltransferase hydrolysis of lipid-linked oligosaccharides in the ER lumen, followed by ENGase and mannosidase processing in the cytosol and lysosomes. Furthermore, synthetic Manβ1-4GlcNAc disaccharide stimulates a broad immune response in vitro, which is in part dependent on the STING-TBK1 pathway, and enhances antibody response in vivo. Together, our data identify Manβ1-4GlcNAc as a novel innate immune modulator associated with chronic autoimmune diseases.
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