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

Kia Joo PuanBoris San LuisNurhashikin YusofDilip KumarAnand Kumar AndiappanWendy LeeSamanta CajicDragana VuckovicJing De ChanTobias DöllnerHan Wei HouYunxuan JiangChao Tiannull nullErdmann RappMichael PoidingerDe Yun WangNicole SoranzoBernett LeeOlaf Rotzschke
Published in: Communications biology (2021)
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.
Keyphrases
  • poor prognosis
  • data analysis
  • genome wide
  • flow cytometry
  • binding protein
  • peripheral blood
  • copy number
  • long non coding rna
  • early onset
  • gene expression
  • transcription factor