Core 1– and 3–derived O -glycans collectively maintain the colonic mucus barrier and protect against spontaneous colitis in mice

MUCOSAL IMMUNOLOGY(2016)

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摘要
Core 1– and 3–derived mucin-type O -glycans are primary components of the mucus layer in the colon. Reduced mucus thickness and impaired O -glycosylation are observed in human ulcerative colitis. However, how both types of O -glycans maintain mucus barrier function in the colon is unclear. We found that C1galt1 expression, which synthesizes core 1 O -glycans, was detected throughout the colon, whereas C3GnT , which controls core 3 O -glycan formation, was most highly expressed in the proximal colon. Consistent with this, mice lacking intestinal core 1–derived O -glycans (IEC C1galt1 −/− ) developed spontaneous colitis primarily in the distal colon, whereas mice lacking both intestinal core 1– and 3–derived O -glycans (DKO) developed spontaneous colitis in both the distal and proximal colon. DKO mice showed an early onset and more severe colitis than IEC C1galt1 −/− mice. Antibiotic treatment restored the mucus layer and attenuated colitis in DKO mice. Mucins from DKO mice were more susceptible to proteolysis than wild-type mucins. This study indicates that core 1– and 3–derived O -glycans collectively contribute to the mucus barrier by protecting it from bacterial protease degradation and suggests new therapeutic targets to promote mucus barrier function in colitis patients.
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关键词
Colitis,Glycoproteins,Medical research,Mucosal immunology,Biomedicine,general,Immunology,Allergology,Antibodies,Gastroenterology
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