ArticleJournal of immunology (Baltimore, Md. : 1950)2013
α3/4 Fucosyltransferase 3-dependent synthesis of Sialyl Lewis A on CD44 variant containing exon 6 mediates polymorphonuclear leukocyte detachment from intestinal epithelium during transepithelial migration.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
- The protein tyrosine phosphatase CD45 promotes PMN transepithelial migration, antimicrobial function, and colonic mucosal repair.JCI insight · 2026Article
- Elevated neuraminidase potentiates lung inflammation through facilitating integrin β2-mediated adhesion and immune responses of neutrophils.The Journal of biological chemistry · 2026Article
- Sialylation regulates neutrophil transepithelial migration, CD11b/CD18 activation, and intestinal mucosal inflammatory function.JCI insight · 2023Article
- Distinct stimulus-dependent neutrophil dynamics revealed by real-time imaging of intestinal mucosa after acute injury.PNAS nexus · 2022Article
- Intestinal Norovirus Binding Patterns in Nonsecretor Individuals.Journal of virology · 2022Article
- Article
- Finding the sweet spot: glycosylation mediated regulation of intestinal inflammation.Mucosal immunology · 2022Review
- LEUKOCYTE-EPITHELIAL INTERACTIONS: A DOUBLE-EDGED SWORD THAT PROTECTS AND INJURES DURING HEALTH AND DISEASE.Transactions of the American Clinical and Climatological Association · 2022Article
- Targeting Aberrantly Elevated Sialyl Lewis A as a Potential Therapy for Impaired Endometrial Selection Ability in Unexplained Recurrent Miscarriage.Frontiers in immunology · 2022Article
- Regulatory mechanisms of neutrophil migration from the circulation to the airspace.Cellular and molecular life sciences : CMLS · 2021Review
- Severe Acute Respiratory Syndrome-Associated Coronavirus 2 Infection and Organ Dysfunction in the ICU: Opportunities for Translational Research.Critical care explorations · 2021Review
- Glycans and Glycan-Binding Proteins as Regulators and Potential Targets in Leukocyte Recruitment.Frontiers in cell and developmental biology · 2021Review
- Intestinal epithelial glycosylation in homeostasis and gut microbiota interactions in IBD.Nature reviews. Gastroenterology & hepatology · 2020Review
- Targeting epithelium-expressed sialyl Lewis glycans improves colonic mucosal wound healing and protects against colitis.JCI insight · 2020Article
- Regulation of neutrophil function by selective targeting of glycan epitopes expressed on the integrin CD11b/CD18.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- How Adhesion Molecule Patterns Change While Neutrophils Traffic through the Lung during Inflammation.Mediators of inflammation · 2019Article
- Novel role of O-glycosyltransferases GALNT3 and B3GNT3 in the self-renewal of pancreatic cancer stem cells.BMC cancer · 2018Article
- Estrogen Receptor-Alpha (ESR1) Governs the Lower Female Reproductive Tract Vulnerability toFrontiers in immunology · 2018Article
- Expression of Lewis-a glycans on polymorphonuclear leukocytes augments function by increasing transmigration.Journal of leukocyte biology · 2017Article
- Pathobiology of neutrophil-epithelial interactions.Immunological reviews · 2016Review
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Polymorphonuclear leukocyte (PMN) migration across the intestinal epithelium closely parallels disease symptoms in patients with inflammatory bowel disease. PMN transepithelial migration (TEM) is a multistep process that terminates with PMN detachment from the apical epithelium into the lumen. Using a unique mAb (GM35), we have previously demonstrated that engagement of the CD44 variant containing exon 6 (CD44v6) blocks both PMN detachment and cleavage of CD44v6. In this article, we report that PMN binding to CD44v6 is mediated by protein-specific O-glycosylation with sialyl Lewis A (sLe(a)). Analyses of glycosyltransferase expression identified fucosyltransferase 3 (Fut3) as the key enzyme driving sLe(a) biosynthesis in human intestinal epithelial cells (IECs). Fut3 transfection of sLe(a)-deficient IECs resulted in robust expression of sLe(a). However, this glycan was not expressed on CD44v6 in these transfected IECs; therefore, engagement of sLe(a) had no effect on PMN TEM across these cells. Analyses of sLe(a) in human colonic mucosa revealed minimal expression in noninflamed areas, with striking upregulation under colitic conditions that correlated with increased expression of CD44v6. Importantly, intraluminal administration of mAb GM35 blocked PMN TEM and attenuated associated increases in intestinal permeability in a murine intestinal model of inflammation. These findings identify a unique role for protein-specific O-glycosylation in regulating PMN-epithelial interactions at the luminal surface of the intestine.
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