Abstract
Sialyl-Lewis x (sLex, CD15s) is a tetra-saccharide on the surface of leukocytes required for E-selectin-mediated rolling, a prerequisite for leukocytes to migrate out of the blood vessels. Here we show using flow cytometry that sLex expression on basophils and mast cell progenitors depends on fucosyltransferase 6 (FUT6). Using genetic association data analysis and qPCR, the cell type-specific defect was associated with single nucleotide polymorphisms (SNPs) in the FUT6 gene region (tagged by rs17855739 and rs778798), affecting coding sequence and/or expression level of the mRNA. Heterozygous individuals with one functional FUT6 gene harbor a mixed population of sLex+ and sLex- basophils, a phenomenon caused by random monoallelic expression (RME). Microfluidic assay demonstrated FUT6-deficient basophils rolling on E-selectin is severely impaired. FUT6 null alleles carriers exhibit elevated blood basophil counts and a reduced itch sensitivity against insect bites. FUT6-deficiency thus dampens the basophil-mediated allergic response in the periphery, evident also in lower IgE titers and reduced eosinophil counts.
Highlights
Sialyl-Lewis x is a tetra-saccharide on the surface of leukocytes required for Eselectin-mediated rolling, a prerequisite for leukocytes to migrate out of the blood vessels
Sialyl Lewis x is a tetra-saccharide composed of N-acetylneuraminic acid, galactose, fucose, and N-acetyl glucosamine (NeuNAcα2,3Galβ1,4(Fucα1,3)GlcNAc). sLex expression has been reported on various leukocytes, including monocytes, neutrophils, activated T cells[1], and regulatory T cells[2]
fucosyltransferase 6 (FUT6) deficiency (OMIM #613852) was originally discovered as a congenital condition characterized by the lack of FUT6 activity in the plasma[7]
Summary
Sialyl-Lewis x (sLex, CD15s) is a tetra-saccharide on the surface of leukocytes required for Eselectin-mediated rolling, a prerequisite for leukocytes to migrate out of the blood vessels. We show using flow cytometry that sLex expression on basophils and mast cell progenitors depends on fucosyltransferase 6 (FUT6). SLex expression has been reported on various leukocytes, including monocytes, neutrophils, activated T cells[1], and regulatory T cells[2]. It forms the terminal group of O-glycans on molecules such as PSGL-1, CD43, or CD44 but is found on. SLex plays a crucial role in extravasation Their transient interaction with E-selectin on activated epithelial surface of blood vessels[3] results in the deceleration of the cell in the blood stream (“rolling”), which allows a firm integrin-dependent adhesion to facilitate trans-endothelial migration[4]. The loss, is compensated by CD65s (VIM-2), a functional sLex paralog generated by FUT4
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
