Intelectin-1 binds and alters the localization of the mucus barrier–modifying bacterium <i>Akkermansia muciniphila</i>
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- Juan D. Matute
- Division of Gastroenterology, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 1
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- Jinzhi Duan
- Division of Gastroenterology, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 1
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- Magdalena B. Flak
- Division of Gastroenterology, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 1
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- Paul Griebel
- Division of Gastroenterology, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 1
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- Jose A. Tascon-Arcila
- Division of Gastroenterology, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 1
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- Shauni Doms
- Guest Group Evolutionary Medicine, Max Planck Institute for Evolutionary Biology, Plön, Germany 4
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- Thomas Hanley
- Division of Gastroenterology, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 1
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- Agne Antanaviciute
- Medical Research Council (MRC) Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK 6
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- Jennifer Gundrum
- The Forsyth Institute, Cambridge, MA 8
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- Jessica L. Mark Welch
- Marine Biological Laboratory, Woods Hole, MA 9
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- Brandon Sit
- Division of Infectious Diseases, Brigham and Women’s Hospital, Boston, MA 10
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- Shabnam Abtahi
- Laboratory of Mucosal Barrier Pathobiology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 14
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- Gwenny M. Fuhler
- Department of Gastroenterology & Hepatology, Erasmus MC, University Medical Center, Rotterdam, Netherlands 15
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- Joep Grootjans
- Division of Gastroenterology, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 1
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- Florian Tran
- Institute of Clinical Molecular Biology, Christian-Albrechts-University and University Hospital Schleswig-Holstein, Kiel, Germany 3
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- Stephanie T. Stengel
- Institute of Clinical Molecular Biology, Christian-Albrechts-University and University Hospital Schleswig-Holstein, Kiel, Germany 3
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- James R. White
- Resphera Biosciences, Baltimore, MD 17
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- Niklas Krupka
- Division of Gastroenterology, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 1
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- Dirk Haller
- Nutrition and Immunology, Technische Universität München, Freising, Germany 18
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- Simon Clare
- Wellcome Trust Sanger Institute, Hinxton, UK 19
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- Trevor D. Lawley
- Wellcome Trust Sanger Institute, Hinxton, UK 19
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- Arthur Kaser
- Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, and Division of Gastroenterology and Hepatology, Department of Medicine, University of Cambridge, Cambridge, UK 20
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- Alison Simmons
- Medical Research Council (MRC) Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK 6
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- Jonathan N. Glickman
- Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 21
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- Lynn Bry
- Massachusetts Host-Microbiome Center, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 22
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- Philip Rosenstiel
- Institute of Clinical Molecular Biology, Christian-Albrechts-University and University Hospital Schleswig-Holstein, Kiel, Germany 3
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- Gary Borisy
- The Forsyth Institute, Cambridge, MA 8
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- Matthew K. Waldor
- Division of Infectious Diseases, Brigham and Women’s Hospital, Boston, MA 10
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- John F. Baines
- Guest Group Evolutionary Medicine, Max Planck Institute for Evolutionary Biology, Plön, Germany 4
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- Jerrold R. Turner
- Laboratory of Mucosal Barrier Pathobiology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 14
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- Richard S. Blumberg
- Division of Gastroenterology, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 1
抄録
<jats:p>Intelectin-1 (ITLN1) is a lectin secreted by intestinal epithelial cells (IECs) and upregulated in human ulcerative colitis (UC). We investigated how ITLN1 production is regulated in IECs and the biological effects of ITLN1 at the host–microbiota interface using mouse models. Our data show that ITLN1 upregulation in IECs from UC patients is a consequence of activating the unfolded protein response. Analysis of microbes coated by ITLN1 in vivo revealed a restricted subset of microorganisms, including the mucolytic bacterium Akkermansia muciniphila. Mice overexpressing intestinal ITLN1 exhibited decreased inner colonic mucus layer thickness and closer apposition of A. muciniphila to the epithelial cell surface, similar to alterations reported in UC. The changes in the inner mucus layer were microbiota and A. muciniphila dependent and associated with enhanced sensitivity to chemically induced and T cell–mediated colitis. We conclude that by determining the localization of a select group of bacteria to the mucus layer, ITLN1 modifies this critical barrier. Together, these findings may explain the impact of ITLN1 dysregulation on UC pathogenesis.</jats:p>
収録刊行物
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- Journal of Experimental Medicine
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Journal of Experimental Medicine 220 (1), 2022-11-22
Rockefeller University Press