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Loss of intestinal ...
Loss of intestinal core 1-derived O-glycans causes spontaneous colitis in mice.
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Fu, Jianxin (author)
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Wei, Bo (author)
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Wen, Tao (author)
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- Johansson, Malin E V, 1971 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
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Liu, Xiaowei (author)
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Bradford, Emily (author)
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- Thomsson, Kristina A, 1969 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
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McGee, Samuel (author)
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Mansour, Lilah (author)
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Tong, Maomeng (author)
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McDaniel, J Michael (author)
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Sferra, Thomas J (author)
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Turner, Jerrold R (author)
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Chen, Hong (author)
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- Hansson, Gunnar C., 1951 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
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Braun, Jonathan (author)
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Xia, Lijun (author)
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(creator_code:org_t)
- 2011
- 2011
- English.
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In: The Journal of clinical investigation. - 1558-8238. ; 121:4, s. 1657-66
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Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Andra medicinska och farmaceutiska grundvetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Other Basic Medicine (hsv//eng)
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- ref (subject category)
- art (subject category)
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- By the author/editor
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Fu, Jianxin
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Wei, Bo
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Wen, Tao
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Johansson, Malin ...
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Liu, Xiaowei
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Bradford, Emily
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show more...
-
Thomsson, Kristi ...
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McGee, Samuel
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Mansour, Lilah
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Tong, Maomeng
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McDaniel, J Mich ...
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Sferra, Thomas J
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Turner, Jerrold ...
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Chen, Hong
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Hansson, Gunnar ...
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Braun, Jonathan
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Xia, Lijun
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Medical Biotechn ...
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and Medical Biotechn ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Other Basic Medi ...
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The Journal of c ...
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University of Gothenburg