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ResearchIn-Press PreviewCell biologyGastroenterology Open Access | 10.1172/jci.insight.181481

MUC17 is an essential small intestinal glycocalyx component that is disrupted in Crohn’s disease

Elena Layunta,1 Sofia Jäverfelt,1 Fleur C. van de Koolwijk,1 Molly Sivertsson,1 Brendan Dolan,1 Liisa Arike,1 Sara I.M. Thulin,1 Bruce A. Vallance,2 and Thaher Pelaseyed1

1Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden

2Division of Gastroenterology, Hepatology and Nutrition, Department of Pedia, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, Canada

Find articles by Layunta, E. in: JCI | PubMed | Google Scholar

1Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden

2Division of Gastroenterology, Hepatology and Nutrition, Department of Pedia, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, Canada

Find articles by Jäverfelt, S. in: JCI | PubMed | Google Scholar

1Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden

2Division of Gastroenterology, Hepatology and Nutrition, Department of Pedia, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, Canada

Find articles by van de Koolwijk, F. in: JCI | PubMed | Google Scholar

1Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden

2Division of Gastroenterology, Hepatology and Nutrition, Department of Pedia, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, Canada

Find articles by Sivertsson, M. in: JCI | PubMed | Google Scholar

1Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden

2Division of Gastroenterology, Hepatology and Nutrition, Department of Pedia, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, Canada

Find articles by Dolan, B. in: JCI | PubMed | Google Scholar

1Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden

2Division of Gastroenterology, Hepatology and Nutrition, Department of Pedia, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, Canada

Find articles by Arike, L. in: JCI | PubMed | Google Scholar |

1Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden

2Division of Gastroenterology, Hepatology and Nutrition, Department of Pedia, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, Canada

Find articles by Thulin, S. in: JCI | PubMed | Google Scholar

1Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden

2Division of Gastroenterology, Hepatology and Nutrition, Department of Pedia, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, Canada

Find articles by Vallance, B. in: JCI | PubMed | Google Scholar

1Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden

2Division of Gastroenterology, Hepatology and Nutrition, Department of Pedia, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, Canada

Find articles by Pelaseyed, T. in: JCI | PubMed | Google Scholar

Published December 19, 2024 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.181481.
Copyright © 2024, Layunta et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published December 19, 2024 - Version history
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Abstract

Crohn's disease (CD) is the chronic inflammation of the terminal ileum and colon triggered by a dysregulated immune response to bacteria, but insights into specific molecular perturbations at the critical bacteria-epithelium interface are limited. Here we report that the membrane mucin MUC17 protected small intestinal enterocytes against commensal and pathogenic bacteria. In non-inflamed CD ileum, reduced MUC17 levels and a compromised glycocalyx barrier allowed recurrent bacterial contact with enterocytes. Muc17 deletion in mice rendered the small intestine particularly prone to atypical bacterial infection while maintaining resistance to colitis. The loss of Muc17 resulted in spontaneous deterioration of epithelial homeostasis and in the extra-intestinal translocation of bacteria. Finally, Muc17-deficient mice harbored specific small intestinal bacterial taxa observed in CD patients. Our findings highlight MUC17 as an essential regiospecific line of defense in the small intestine with relevance for early epithelial defects in CD.

Graphical Abstract
graphical abstract
Supplemental material

View Unedited blot and gel images

View Supplemental Table 1. Clinical information and metadata for enrolled subjects

View Supplemental Table 2. Proteomic profiling of intestinal epithelial cells

View Supplemental Table 3. Primer sequences for 16S V3/V4 amplicon library preparation and Index sequences for Adapterama scheme

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Version history
  • Version 1 (December 19, 2024): In-Press Preview
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