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Loss of intestinal core 1–derived O-glycans causes spontaneous colitis in mice
Open accessAbstract
Mucin-type O-linked oligosaccharides (O-glycans) are primary components of the intestinal mucins that form the mucus gel layer overlying the gut epithelium. Impaired expression of intestinal O-glycans has been observed in patients with ulcerative colitis (UC), but its role in the etiology of this disease is unknown. Here, we report that mice with intestinal epithelial cell-specific deficiency of core 1-derived O-glycans, the predominant form of O-glycans, developed spontaneous colitis that resembled human UC, including massive myeloid infiltrates and crypt abscesses. The colitis manifested in these mice was also characterized by TNF-producing myeloid infiltrates in colon mucosa in the absence of lymphocytes, supporting an essential role for myeloid cells in colitis initiation. Furthermore, induced deletion of intestinal core 1-derived O-glycans caused spontaneous colitis in adult mice. These data indicate a causal role for the loss of core 1-derived O-glycans in colitis. Finally, we detected a biosynthetic intermediate typically exposed in the absence of core 1 O-glycan, Tn antigen, in the colon epithelium of a subset of UC patients. Somatic mutations in the X-linked gene that encodes core 1 β1,3-galactosyltransferase-specific chaperone 1 (C1GALT1C1, also known as Cosmc), which is essential for core 1 O-glycosylation, were found in Tn-positive epithelia. These data suggest what we believe to be a new molecular mechanism for the pathogenesis of UC.
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“The importance of sufficiently complex mucin glycans was demonstrated in studies of mice with truncated glycans as found in O-glycan core 1 or core 3 deficient mice 19, 28.”
From The composition of the gut microbiota shapes the colon mucus barrier (2015) · cites this paper as [19]
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Metadata
- Authors
- Fu, J., Wei, B., Wen, T., Johansson, M. E. V., Liu, X., Bradford, E., Thomsson, K. A., McGee, S., Mansour, L., Tong, M., McDaniel, J. M., Sferra, T. J., Turner, J. R., Chen, H., Hansson, G. C., Braun, J., & Xia, L.
- Affiliations
- Oklahoma Medical Research Foundation (US)
- University of California, Los Angeles (US)
- University of Gothenburg (SE)
- Central South University (CN)
- University of Chicago (US)
- University of Oklahoma (US)
- Corresponding author
- Xia, Lijun
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2011-04-01
- Volume
- 121
- Issue
- 4
- Pages
- 1657-1666
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC3069788
- OpenAlex
- W2051146429
- Cited by
- 366
- References
- 59
- Citations by year
- 2026: 19 · 2025: 21 · 2024: 29 · 2023: 21 · 2022: 18 · 2021: 30 · 2020: 21 · 2019: 15 · 2018: 27 · 2017: 22 · 2016: 24 · 2015: 32 · 2014: 37 · 2013: 25 · 2012: 16
- FWCI
- 11.16
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Oklahoma Medical Research Foundation
- Stiftelsen för Strategisk Forskning
- Central South University
- Xiangya Hospital, Central South University
- National Institute of Allergy and Infectious Diseases (U01AI095473)
- National Institute of Diabetes and Digestive and Kidney Diseases (P01DK046763, P01DK067887, R56DK094954, R01DK085691, R01DK061931)
- National Center for Research Resources (RR 018758, P20RR018758)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Health Sciences › Medicine › Gastroenterology › Inflammatory Bowel Disease
- Physical Sciences › Chemistry › Organic Chemistry › Carbohydrate Chemistry and Synthesis
- Keywords
- core 1 O-glycans, ulcerative colitis, spontaneous colitis, intestinal epithelial cells, Tn antigen, Cosmc, crypt abscesses, TNF-α, colonic mucus, colitis pathogenesis, X-linked mutations
- MeSH terms
- Animals, Base Sequence, Colitis, Colon, Disease Models, Animal, Galactosyltransferases, Humans, Intestinal Mucosa, Mice, Inbred C57BL, Mice, Transgenic, Mutation, Polysaccharides, Antigens, Tumor-Associated, Carbohydrate, DNA Primers, Mice, Knockout, Molecular Chaperones, Mice, Mice, 129 Strain
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