A bioactive mammalian disaccharide associated with autoimmunity activates STING-TBK1-dependent immune response
Identifieur interne : 000B38 ( Main/Exploration ); 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
Affiliations:
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Lehrman</name><affiliation wicri:level="2"><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9482 7121</institution-id><institution-id institution-id-type="GRID">grid.267313.2</institution-id><institution>Department of Pharmacology, Department of Microbiology,</institution><institution>University of Texas Southwestern Medical Center,</institution></institution-wrap>Dallas, TX 75390 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Texas</region></placeName><wicri:cityArea>Dallas</wicri:cityArea></affiliation></author><author><name sortKey="Matsuo, Ichiro" sort="Matsuo, Ichiro" uniqKey="Matsuo I" first="Ichiro" last="Matsuo">Ichiro Matsuo</name><affiliation wicri:level="1"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9269 4097</institution-id><institution-id institution-id-type="GRID">grid.256642.1</institution-id><institution>Division of Molecular Science,</institution><institution>Gunma University,</institution></institution-wrap>Maebashi, 371-8510 Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Maebashi</wicri:regionArea></affiliation></author><author><name sortKey="Yan, Nan" sort="Yan, Nan" uniqKey="Yan N" first="Nan" last="Yan">Nan Yan</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9482 7121</institution-id><institution-id institution-id-type="GRID">grid.267313.2</institution-id><institution>Department of Immunology,</institution><institution>University of Texas Southwestern Medical Center,</institution></institution-wrap>Dallas, TX 75390 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Texas</region></placeName><wicri:cityArea>Dallas</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="Aff6"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9482 7121</institution-id><institution-id institution-id-type="GRID">grid.267313.2</institution-id><institution>Department of Microbiology,</institution><institution>University of Texas Southwestern Medical Center,</institution></institution-wrap>Dallas, TX 75390 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Texas</region></placeName><wicri:cityArea>Dallas</wicri:cityArea></affiliation></author></analytic><series><title level="j">Nature Communications</title><idno type="eISSN">2041-1723</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><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></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Sancho, D" uniqKey="Sancho D">D Sancho</name></author><author><name sortKey="Reis E Sousa, C" uniqKey="Reis E Sousa C">C Reis e Sousa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rabinovich, Ga" uniqKey="Rabinovich G">GA Rabinovich</name></author><author><name sortKey="Van Kooyk, Y" uniqKey="Van Kooyk Y">Y van Kooyk</name></author><author><name sortKey="Cobb, Ba" uniqKey="Cobb B">BA Cobb</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Green, Rs" uniqKey="Green R">RS Green</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yan, N" uniqKey="Yan N">N Yan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hasan, M" uniqKey="Hasan 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Boraston</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gao, N" uniqKey="Gao N">N Gao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhu, M" uniqKey="Zhu M">M Zhu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Pelt, J" uniqKey="Van Pelt J">J van Pelt</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Riise Stensland, Hmf" uniqKey="Riise Stensland H">HMF Riise Stensland</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhu, M" uniqKey="Zhu M">M Zhu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hasan, M" uniqKey="Hasan M">M Hasan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hirayama, H" uniqKey="Hirayama H">H Hirayama</name></author><author><name sortKey="Seino, J" uniqKey="Seino J">J Seino</name></author><author><name sortKey="Kitajima, T" uniqKey="Kitajima T">T Kitajima</name></author><author><name sortKey="Jigami, Y" uniqKey="Jigami Y">Y Jigami</name></author><author><name sortKey="Suzuki, T" uniqKey="Suzuki T">T Suzuki</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hossain, T" uniqKey="Hossain T">T Hossain</name></author><author><name sortKey="Hirayama, H" uniqKey="Hirayama H">H Hirayama</name></author><author><name sortKey="Harada, Y" uniqKey="Harada Y">Y Harada</name></author><author><name sortKey="Suzuki, T" uniqKey="Suzuki T">T Suzuki</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Suzuki, T" uniqKey="Suzuki T">T Suzuki</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Japon</li><li>États-Unis</li></country><region><li>Texas</li></region></list><tree><country name="États-Unis"><region name="Texas"><name sortKey="Fermaintt, Charles S" sort="Fermaintt, Charles S" uniqKey="Fermaintt C" first="Charles S." last="Fermaintt">Charles S. Fermaintt</name></region><name sortKey="Dobbs, Nicole" sort="Dobbs, Nicole" uniqKey="Dobbs N" first="Nicole" last="Dobbs">Nicole Dobbs</name><name sortKey="Fu, Yang Xin" sort="Fu, Yang Xin" uniqKey="Fu Y" first="Yang-Xin" last="Fu">Yang-Xin Fu</name><name sortKey="Lehrman, Mark A" sort="Lehrman, Mark A" uniqKey="Lehrman M" first="Mark A." last="Lehrman">Mark A. Lehrman</name><name sortKey="Liu, Zhida" sort="Liu, Zhida" uniqKey="Liu Z" first="Zhida" last="Liu">Zhida Liu</name><name sortKey="Yan, Nan" sort="Yan, Nan" uniqKey="Yan N" first="Nan" last="Yan">Nan Yan</name><name sortKey="Yan, Nan" sort="Yan, Nan" uniqKey="Yan N" first="Nan" last="Yan">Nan Yan</name></country><country name="Japon"><noRegion><name sortKey="Sano, Kanae" sort="Sano, Kanae" uniqKey="Sano K" first="Kanae" last="Sano">Kanae Sano</name></noRegion><name sortKey="Ishii, Nozomi" sort="Ishii, Nozomi" uniqKey="Ishii N" first="Nozomi" last="Ishii">Nozomi Ishii</name><name sortKey="Matsuo, Ichiro" sort="Matsuo, Ichiro" uniqKey="Matsuo I" first="Ichiro" last="Matsuo">Ichiro Matsuo</name><name sortKey="Seino, Junichi" sort="Seino, Junichi" uniqKey="Seino J" first="Junichi" last="Seino">Junichi Seino</name><name sortKey="Suzuki, Tadashi" sort="Suzuki, Tadashi" uniqKey="Suzuki T" first="Tadashi" last="Suzuki">Tadashi Suzuki</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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