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

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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Fermaintt CS,Sano K,Liu Z,Ishii N,Seino J,Dobbs N,Suzuki T,Fu YX,Lehrman MA,Matsuo I,Yan N

doi

10.1038/s41467-019-10319-5

subject

Has Abstract

pub_date

2019-05-30 00:00:00

pages

2377

issue

1

issn

2041-1723

pii

10.1038/s41467-019-10319-5

journal_volume

10

pub_type

杂志文章

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