A bioactive mammalian disaccharide associated with autoimmunity activates STING-TBK1-dependent immune response
Identifieur interne : 000B38 ( Main/Merge ); précédent : 000B37; suivant : 000B39A bioactive mammalian disaccharide associated with autoimmunity activates STING-TBK1-dependent immune response
Auteurs : Charles S. Fermaintt [États-Unis] ; Kanae Sano [Japon] ; Zhida Liu [États-Unis] ; Nozomi Ishii [Japon] ; Junichi Seino [Japon] ; Nicole Dobbs [États-Unis] ; Tadashi Suzuki [Japon] ; Yang-Xin Fu [États-Unis] ; Mark A. Lehrman [États-Unis] ; Ichiro Matsuo [Japon] ; Nan Yan [États-Unis]Source :
- Nature Communications [ 2041-1723 ] ; 2019.
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
Url:
DOI: 10.1038/s41467-019-10319-5
PubMed: 31147550
PubMed Central: 6542856
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PMC:6542856Le document en format XML
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<front><div type="abstract" xml:lang="en"><p id="Par1">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 <italic>TREX1</italic>
-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.</p>
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