ArticleThe Journal of experimental medicine2023
Intelectin-1 binds and alters the localization of the mucus barrier-modifying bacterium Akkermansia muciniphila.
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Article in The Journal of experimental medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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22citing papers in PubMed, 1 pooled it
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22 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
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- Research progress on intestinal probiotics-mediated protection of the intestinal mucosal barrier in ulcerative colitis.Frontiers in immunology · 2026Review
- Integrated Single Cell Spatial Analysis Reveals Dysregulated Basal Progenitor Cells in Ulcerative Colitis Pathogenesis: A Multi Omics Study.Health science reports · 2026Article
- Navigating the duality of Akkermansia muciniphila.Nature microbiology · 2026Review
- Modified gegen qinlian decoction amelioratesFrontiers in pharmacology · 2026Article
- Exploring the role of intelectin-1 in modulating asthma through the gut-bone-lung axis.Gut microbes · 2025Article
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- Akkermansia muciniphila: a microbial guardian against oxidative stress-gut microbiota crosstalk and clinical prospects.Journal of translational medicine · 2025Review
- Activation of STAT6 in Intestinal Epithelial Cells Predisposes to Gut Inflammation.European journal of immunology · 2025Article
- ITLN1 exacerbates Crohn's colitis by driving ZBP1-dependent PANoptosis in intestinal epithelial cells through antagonizing TRIM8-mediated CAPN2 ubiquitination.International journal of biological sciences · 2025Article
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Authors and funding
31 authors at 11 institutions in 4 countries.
Juan D Matute *Division of Gastroenterology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0002-1703-8115
Jinzhi Duan *Division of Gastroenterology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0001-9351-4956
Magdalena B Flak *Division of Gastroenterology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0002-8238-9835
Paul GriebelDivision of Gastroenterology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0001-5671-8183
Jose A Tascon-ArcilaDivision of Gastroenterology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0001-6647-2842
Shauni DomsGuest Group Evolutionary Medicine, Max Planck Institute for Evolutionary Biology, Plön, Germany.ORCID 0000-0002-2129-4138
Thomas HanleyDivision of Gastroenterology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0002-4270-8299
Agne AntanaviciuteMedical Research Council (MRC) Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.ORCID 0000-0002-9019-2215
Jennifer GundrumThe Forsyth Institute, Cambridge, MA.ORCID 0000-0001-8136-2537
Jessica L Mark WelchMarine Biological Laboratory, Woods Hole, MA.ORCID 0000-0003-0696-2334
Brandon SitDivision of Infectious Diseases, Brigham and Women's Hospital, Boston, MA.ORCID 0000-0003-2378-3039
Shabnam AbtahiLaboratory of Mucosal Barrier Pathobiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.ORCID 0000-0003-3096-8023
Gwenny M FuhlerDepartment of Gastroenterology & Hepatology, Erasmus MC, University Medical Center, Rotterdam, Netherlands.ORCID 0000-0001-9221-4855
Joep GrootjansDivision of Gastroenterology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0002-2805-4831
Florian TranInstitute of Clinical Molecular Biology, Christian-Albrechts-University and University Hospital Schleswig-Holstein, Kiel, Germany.ORCID 0000-0002-3735-9872
Stephanie T StengelInstitute of Clinical Molecular Biology, Christian-Albrechts-University and University Hospital Schleswig-Holstein, Kiel, Germany.ORCID 0000-0003-2949-879X
James R WhiteResphera Biosciences, Baltimore, MD.ORCID 0000-0002-7535-9179
Niklas KrupkaDivision of Gastroenterology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0001-5948-7536
Dirk HallerNutrition and Immunology, Technische Universität München, Freising, Germany.ORCID 0000-0002-6977-4085
Simon ClareWellcome Trust Sanger Institute, Hinxton, UK.ORCID 0000-0001-9368-6037
Trevor D LawleyWellcome Trust Sanger Institute, Hinxton, UK.ORCID 0000-0002-4805-621X
Arthur KaserCambridge 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.ORCID 0000-0003-1419-3344
Alison SimmonsMedical Research Council (MRC) Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.ORCID 0000-0003-3454-0710
Jonathan N GlickmanDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.ORCID 0000-0003-0910-2655
Lynn BryMassachusetts Host-Microbiome Center, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0002-8792-8527
Philip RosenstielInstitute of Clinical Molecular Biology, Christian-Albrechts-University and University Hospital Schleswig-Holstein, Kiel, Germany.ORCID 0000-0002-9692-8828
Gary BorisyThe Forsyth Institute, Cambridge, MA.ORCID 0000-0002-0266-8018
Matthew K WaldorDivision of Infectious Diseases, Brigham and Women's Hospital, Boston, MA.ORCID 0000-0003-1843-7000
John F BainesGuest Group Evolutionary Medicine, Max Planck Institute for Evolutionary Biology, Plön, Germany.ORCID 0000-0002-8132-4909
Jerrold R Turner *Laboratory of Mucosal Barrier Pathobiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.ORCID 0000-0003-0627-9455
Richard S Blumberg *Division of Gastroenterology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0002-9704-248X
Brigham and Women's Hospital · USUniversity Hospital Schleswig-Holstein · DEChristian-Albrechts-Universität zu Kiel · DEJohn Radcliffe Hospital · GBWellcome Sanger Institute · GBBeth Israel Deaconess Medical Center · USErasmus MC · NLMarine Biological Laboratory · USResphera Biosciences · USTechnical University of Munich · DEUniversity of Cambridge · GB
Funding
Pediatric Scientist Development Program (PSDP) [K12]K12HD000850 · NICHD · YALE UNIVERSITY · PI Sallie R. Permar · 1987 to 2026
$44.1MSTRUCTURE-FUNCTION RELATIONSHIPS IN THE ALIMENTARY TRACTP30DK034854 · NIDDK · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI JONATHAN C KAGAN · 1986 to 2026
$32.4MZO-1-MEDIATED PROTEIN INTERACTIONS: REGULATORS AND INTEGRATORS OF DIVERSE EPITHELIAL FUNCTIONS IN HEALTH AND DISEASER01DK061931 · NIDDK · UNIVERSITY OF CHICAGO · PI JERROLD R. TURNER · 2001 to 2026
$15.0MRegulation of Mucosal LymphocytesR01DK051362 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI Richard S Blumberg, Yu-Hwa Huang Blumberg · 1997 to 2026
$13.5MTherapeutic targeting of protein interactions to reverse MLCK1-mediated intestinal barrier loss and ameliorate disease.R01DK068271 · NIDDK · UNIVERSITY OF CHICAGO · PI JERROLD R. TURNER · 2005 to 2026
$11.3MINTESTINAL TRANSCYTOSIS OF IGG IN ADULT LIFER01DK053056 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI BLUMBERG, RICHARD S · 1997 to 2021
$10.6MMOLECULAR CHARACTERIZATION OF MUCOSAL LYMPHOCYTESR01DK044319 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI Richard S Blumberg · 1992 to 2026
$10.4MEndoplasmic reticulum stress and intestinal inflammationR01DK088199 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI Richard S Blumberg · 2010 to 2026
$9.6MSpatial Organization of the Oral MicrobiomeR01DE022586 · NIDCR · MARINE BIOLOGICAL LABORATORY · PI Jessica Leigh Mark Welch · 2013 to 2026
$8.7MVibrio cholerae intestinal colonization and vaccine developmentR01AI042347 · NIAID · TUFTS UNIVERSITY BOSTON · PI WALDOR, MATTHEW K · 1998 to 2025
$7.3MCharacterization of Mucosal LymphocytesR37DK044319 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI BLUMBERG, RICHARD S · 2005 to 2014
$7.2MIntestinal Intelectin-1 regulation of obesity developmentK08DK133639 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI Juan D. Matute · 2023 to 2026
$664kMedical Research Council MC_PC_MR/S025952/1Medical Research Council MC_UU_00008/7Medical Research Council MC_UU_12010/7Medical Research Council MR/S036377/1NIAID NIH HHS R01 AI042347NICHD NIH HHS K12 HD000850NIDCR NIH HHS R01 DE022586NIDDK NIH HHS K08 DK133639NIDDK NIH HHS P30 DK034854NIDDK NIH HHS R01 DK044319NIDDK NIH HHS R01 DK051362NIDDK NIH HHS R01 DK053056NIDDK NIH HHS R01 DK061931NIDDK NIH HHS R01 DK068271NIDDK NIH HHS R01 DK088199NIDDK NIH HHS R37 DK044319NIDDK NIH HHS R56 DK053056NIH HHS DK044319Wellcome Trust 106260/Z/14/ZWellcome Trust 206194
Abstract
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.
Indexed as
Colitis, UlcerativeVerrucomicrobiaAkkermansiaAnimalsHumansLectinsMiceMucusLectins
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