FUT6 deficiency compromises basophil function by selectively abrogating their sialyl-Lewis x expression

Sialyl-Lewis x (sLe x , 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 sLe x 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 sLe x+ and sLe x- 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.