| Title: |
Core fucosylation of IL-2RB is required for natural killer cell homeostasis |
| Authors: |
Sudholz, H; Meng, X; Park, HY; Shen, Z; Nikolic, I; Cursons, J; Goddard-Borger, ED; Schuster, IS; Andoniou, CE; Degli-Esposti, MA; Scott, NE; Chopin, M; Rautela, J; Scheer, S; Huntington, ND |
| Publisher Information: |
Elsevier BV |
| Publication Year: |
2025 |
| Collection: |
The University of Melbourne: Digital Repository |
| Description: |
Natural killer (NK) cell homeostasis and effector functions require context-dependent signaling via numerous receptors, including the interleukin-15 receptor (IL-15R). Post-translational modifications can regulate receptor signaling, impacting receptor turnover and trafficking. Core fucosylation is one such modification known to impact receptor expression and is uniquely mediated by fucosyltransferase 8 (FUT8). We identified FUT8 as an essential gene required for IL-15R responsiveness in a human NK cell genome-wide CRISPR screen. To further validate core fucosylation in IL-15R signaling and NK cell biology, mice lacking Fut8 in NK cells (Fut8fl/flNcr1cre/+) were generated. The loss of core fucose in murine NK cells resulted in severe NK cell lymphopenia, with a reduction in IL-15Rβ (IL-2RB/CD122) expression, impairing in vivo homeostatic proliferation. The loss of FUT8 also decreased NK cell cytotoxicity, tumor immunity, and early viral immunity. Taking these results together, we have identified FUT8 as a key modulator of NK cell biology by regulating their development, IL-15R expression, and signaling. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
2639-1856 |
| Relation: |
https://hdl.handle.net/11343/363032 |
| Availability: |
https://hdl.handle.net/11343/363032 |
| Rights: |
https://creativecommons.org/licenses/by/4.0 ; CC BY |
| Accession Number: |
edsbas.FDEABC4D |
| Database: |
BASE |