FUT6 deficiency compromises basophil function by selectively abrogating their sialyl-Lewis x expression
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 fucosy...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2022
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| Online Access: | https://hdl.handle.net/10356/154951 |
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| author | Puan, Kia Joo San Luis, Boris Nurhashikin Yusof Kumar, Dilip Andiappan, Anand Kumar Lee, Wendy Cajic, Samanta Vuckovic, Dragana Chan, Jing De Döllner, Tobias Hou, Han Wei Jiang, Yunxuan Tian, Chao Rapp, Erdmann Poidinger, Michael Wang, De Yun Soranzo, Nicole Lee, Bernett Rötzschke, Olaf |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Puan, Kia Joo San Luis, Boris Nurhashikin Yusof Kumar, Dilip Andiappan, Anand Kumar Lee, Wendy Cajic, Samanta Vuckovic, Dragana Chan, Jing De Döllner, Tobias Hou, Han Wei Jiang, Yunxuan Tian, Chao Rapp, Erdmann Poidinger, Michael Wang, De Yun Soranzo, Nicole Lee, Bernett Rötzschke, Olaf |
| author_sort | Puan, Kia Joo |
| collection | NTU |
| description | 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. |
| first_indexed | 2024-10-01T06:56:34Z |
| format | Journal Article |
| id | ntu-10356/154951 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T06:56:34Z |
| publishDate | 2022 |
| record_format | dspace |
| spelling | ntu-10356/1549512022-05-27T02:34:07Z FUT6 deficiency compromises basophil function by selectively abrogating their sialyl-Lewis x expression Puan, Kia Joo San Luis, Boris Nurhashikin Yusof Kumar, Dilip Andiappan, Anand Kumar Lee, Wendy Cajic, Samanta Vuckovic, Dragana Chan, Jing De Döllner, Tobias Hou, Han Wei Jiang, Yunxuan Tian, Chao Rapp, Erdmann Poidinger, Michael Wang, De Yun Soranzo, Nicole Lee, Bernett Rötzschke, Olaf Lee Kong Chian School of Medicine (LKCMedicine) School of Mechanical and Aerospace Engineering Science::Medicine Engineering::Mechanical engineering Mast-Cells T-Cells 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. Agency for Science, Technology and Research (A*STAR) National Medical Research Council (NMRC) Published version This 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. 2022-05-27T02:34:06Z 2022-05-27T02:34:06Z 2021 Journal Article Puan, 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-. https://dx.doi.org/10.1038/s42003-021-02295-8 2399-3642 https://hdl.handle.net/10356/154951 10.1038/s42003-021-02295-8 34215830 2-s2.0-85111793618 1 4 832 en SIgN-06-006 SIgN-08-020 SIgN-10-029 BMRC IAF 311006 H16/99/b0/011 NMRC/1150/2008 Communications Biology © 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 http://creativecommons.org/ licenses/by/4.0/. application/pdf |
| spellingShingle | Science::Medicine Engineering::Mechanical engineering Mast-Cells T-Cells Puan, Kia Joo San Luis, Boris Nurhashikin Yusof Kumar, Dilip Andiappan, Anand Kumar Lee, Wendy Cajic, Samanta Vuckovic, Dragana Chan, Jing De Döllner, Tobias Hou, Han Wei Jiang, Yunxuan Tian, Chao Rapp, Erdmann Poidinger, Michael Wang, De Yun Soranzo, Nicole Lee, Bernett Rötzschke, Olaf FUT6 deficiency compromises basophil function by selectively abrogating their sialyl-Lewis x expression |
| title | FUT6 deficiency compromises basophil function by selectively abrogating their sialyl-Lewis x expression |
| title_full | FUT6 deficiency compromises basophil function by selectively abrogating their sialyl-Lewis x expression |
| title_fullStr | FUT6 deficiency compromises basophil function by selectively abrogating their sialyl-Lewis x expression |
| title_full_unstemmed | FUT6 deficiency compromises basophil function by selectively abrogating their sialyl-Lewis x expression |
| title_short | FUT6 deficiency compromises basophil function by selectively abrogating their sialyl-Lewis x expression |
| title_sort | fut6 deficiency compromises basophil function by selectively abrogating their sialyl lewis x expression |
| topic | Science::Medicine Engineering::Mechanical engineering Mast-Cells T-Cells |
| url | https://hdl.handle.net/10356/154951 |
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