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dc.contributor.authorPuan, Kia Jooen_US
dc.contributor.authorSan Luis, Borisen_US
dc.contributor.authorNurhashikin Yusofen_US
dc.contributor.authorKumar, Dilipen_US
dc.contributor.authorAndiappan, Anand Kumaren_US
dc.contributor.authorLee, Wendyen_US
dc.contributor.authorCajic, Samantaen_US
dc.contributor.authorVuckovic, Draganaen_US
dc.contributor.authorChan, Jing Deen_US
dc.contributor.authorDöllner, Tobiasen_US
dc.contributor.authorHou, Han Weien_US
dc.contributor.authorJiang, Yunxuanen_US
dc.contributor.authorTian, Chaoen_US
dc.contributor.authorRapp, Erdmannen_US
dc.contributor.authorPoidinger, Michaelen_US
dc.contributor.authorWang, De Yunen_US
dc.contributor.authorSoranzo, Nicoleen_US
dc.contributor.authorLee, Bernetten_US
dc.contributor.authorRötzschke, Olafen_US
dc.identifier.citationPuan, K. J., San Luis, B., Nurhashikin Yusof, Kumar, D., Andiappan, A. K., Lee, W., Cajic, S., Vuckovic, D., Chan, J. D., Döllner, T., Hou, H. W., Jiang, Y., Tian, C., Rapp, E., Poidinger, M., Wang, D. Y., Soranzo, N., Lee, B. & Rötzschke, O. (2021). FUT6 deficiency compromises basophil function by selectively abrogating their sialyl-Lewis x expression. Communications Biology, 4(1), 832-.
dc.description.abstractSialyl-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.en_US
dc.description.sponsorshipAgency for Science, Technology and Research (A*STAR)en_US
dc.description.sponsorshipNational Medical Research Council (NMRC)en_US
dc.relationBMRC IAF 311006en_US
dc.relation.ispartofCommunications Biologyen_US
dc.rights© 2021 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit licenses/by/4.0/.en_US
dc.subjectEngineering::Mechanical engineeringen_US
dc.titleFUT6 deficiency compromises basophil function by selectively abrogating their sialyl-Lewis x expressionen_US
dc.typeJournal Articleen
dc.contributor.schoolLee Kong Chian School of Medicine (LKCMedicine)en_US
dc.contributor.schoolSchool of Mechanical and Aerospace Engineeringen_US
dc.description.versionPublished versionen_US
dc.description.acknowledgementThis work was supported by grants from the Singapore Immunology Network (SIgN-06- 006, SIgN-08-020, and SIgN-10-029), the National Medical Research Council (NMRC/ 1150/2008) Singapore, and Agency for Science, Technology and Research (A*STAR), Singapore. The SIgN Immunomonitoring platform supported by a BMRC IAF 311006 grant and BMRC transition funds #H16/99/b0/011.en_US
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