2. Academic Validation
  3. FUT6 deficiency compromises basophil function by selectively abrogating their sialyl-Lewis x expression

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

  • Commun Biol. 2021 Jul 2;4(1):832. doi: 10.1038/s42003-021-02295-8.
Kia Joo Puan # 1 2,  Boris San Luis # 1,  Nurhashikin Yusof 1,  Dilip Kumar 1,  Anand Kumar Andiappan 1,  Wendy Lee 1,  Samanta Cajic 3,  Dragana Vuckovic 4,  Jing De Chan 1,  Tobias Döllner 1,  Han Wei Hou 5 6,  Yunxuan Jiang 7,  Chao Tian 7,  23andMe Research Team,  Erdmann Rapp 3 8,  Michael Poidinger 1,  De Yun Wang 9,  Nicole Soranzo 4,  Bernett Lee 1,  Olaf Rötzschke 10
Affiliations

Affiliations

  • 1 Singapore Immunology Network (SIgN), A*STAR (Agency for Science, Technology and Research), Singapore, Singapore.
  • 2 Shanghai Junshi Biosciences Co., Ltd, Shanghai, China.
  • 3 Max Planck Institute for Dynamics of Complex Technical Systems, Magdeburg, Germany.
  • 4 Department of Human Genetics, Wellcome Sanger Institute, Cambridge, UK.
  • 5 Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
  • 6 School of Mechanical and Aerospace Engineering, Nanyang Technological University, Singapore, Singapore.
  • 7 23andMe, Inc., Sunnyvale, CA, USA.
  • 8 glyXera GmbH, Magdeburg, Germany.
  • 9 Department of Otolaryngology, National University of Singapore, Singapore, Singapore.
  • 10 Singapore Immunology Network (SIgN), A*STAR (Agency for Science, Technology and Research), Singapore, Singapore. olaf_rotzschke@immunol.a-star.edu.sg.
  • # Contributed equally.
PMID: 34215830 DOI: 10.1038/s42003-021-02295-8
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.

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