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

Area of Science:

• Immunology
• Glycobiology
• Genetics

Background:

• Sialyl-Lewis x (sLe^x) is crucial for leukocyte E-selectin-mediated rolling and extravasation.
• Basophils and mast cell progenitors express sLe^x, but the regulatory mechanisms are not fully understood.

Purpose of the Study:

• To investigate the role of fucosyltransferase 6 (FUT6) in sLe^x expression on basophils and mast cell progenitors.
• To determine the functional consequences of FUT6 deficiency on basophil function and allergic responses.

Main Methods:

• Flow cytometry to assess sLe^x expression.
• Genetic association analysis and qPCR to identify FUT6 gene variations.
• Microfluidic assays to evaluate basophil rolling on E-selectin.
• Analysis of blood basophil counts, IgE titers, and eosinophil counts in FUT6-deficient individuals.

Main Results:

• sLe^x expression on basophils and mast cell progenitors is dependent on FUT6.
• SNPs in the FUT6 gene region (rs17855739, rs778798) are associated with altered sLe^x expression.
• FUT6-deficient basophils show impaired rolling on E-selectin.
• FUT6 null allele carriers have elevated blood basophil counts, reduced itch sensitivity, lower IgE titers, and reduced eosinophil counts.

Conclusions:

• FUT6 is essential for sLe^x expression on basophils and mast cell progenitors.
• FUT6 deficiency dampens peripheral basophil-mediated allergic responses.
• FUT6 variations may influence susceptibility to allergic conditions and insect bite hypersensitivity.