In:
Communications Biology, Springer Science and Business Media LLC, Vol. 4, No. 1 ( 2021-07-02)
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
2399-3642
DOI:
10.1038/s42003-021-02295-8
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2021
detail.hit.zdb_id:
2919698-X