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Sulfation at Glycopolymer Side Chains Switches Activity at the Macrophage Mannose Receptor (CD206) In Vitro and In Vivo

Mastrotto, Francesca; Pirazzini, Marco; Negro, Samuele; Salama, Alan; Martinez-Pomares, Luisa; Mantovani, Giuseppe

Sulfation at Glycopolymer Side Chains Switches Activity at the Macrophage Mannose Receptor (CD206) In Vitro and In Vivo Thumbnail


Authors

Francesca Mastrotto

Marco Pirazzini

Samuele Negro

Alan Salama



Abstract

The mannose receptor (CD206) is an endocytic receptor expressed by selected innate immune cells and nonvascular endothelium, which plays a critical role in both homeostasis and pathogen recognition. Although its involvement in the development of several diseases and viral infections is well established, molecular tools able to both provide insight on the chemistry of CD206-ligand interactions and, importantly, effectively modulate its activity are currently lacking. Using novel SO4-3-Gal-glycopolymers targeting its cysteine-rich lectin ectodomain, this study uncovers and elucidates a previously unknown mechanism of CD206 blockade involving the formation of stable intracellular SO4-3-Gal-glycopolymer–CD206 complexes that prevents receptor recycling to the cell membrane. Further, we show that SO4-3-Gal glycopolymers inhibit CD206 both in vitro and in vivo, revealing hitherto unknown receptor function and demonstrating their potential as CD206 modulators within future immunotherapies.

Journal Article Type Article
Acceptance Date Nov 19, 2022
Online Publication Date Dec 6, 2022
Publication Date Dec 21, 2022
Deposit Date Jan 24, 2023
Publicly Available Date Jan 26, 2023
Print ISSN 0002-7863
Electronic ISSN 1520-5126
Peer Reviewed Peer Reviewed
Volume 144
Issue 50
Pages 23134–23147
DOI https://doi.org/10.1021/jacs.2c10757
Public URL https://nottingham-repository.worktribe.com/output/14885031
Publisher URL https://pubs.acs.org/doi/10.1021/jacs.2c10757

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