Sulfation at Glycopolymer Side Chains Switches Activity at the Macrophage Mannose Receptor (CD206) In Vitro and In Vivo.
Sulfation at Glycopolymer Side Chains Switches Activity at the Macrophage Mannose Receptor (CD206) In Vitro and In Vivo.
复制标题
体外和体内巨噬细胞甘露糖受体（CD206）侧链巯基化改变活性
DOI：
10.1021/jacs.2c10757
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发表时间：
2022-12-21
影响因子：
15
通讯作者：
Mantovani G
中科院分区：
文献类型：
--
作者：
Mastrotto F;Pirazzini M;Negro S;Salama A;Martinez-Pomares L;Mantovani G
甘露糖受体（CD206）是一种由先天免疫细胞和非血管内皮表达的内吞受体，在体内稳态和病原体识别中起关键作用。虽然它参与了几种疾病和病毒感染的发展，但目前缺乏能够提供cd206 -配体相互作用化学的分子工具，更重要的是，有效调节其活性的分子工具。利用新型so4 -3- gal - gly共聚物靶向富含半胱氨酸的凝集素外结构域，本研究揭示并阐明了CD206阻断的一个先前未知的机制，该机制涉及形成稳定的细胞内so4 -3- gal - gly共聚物- CD206复合物，阻止受体再循环到细胞膜。此外，我们发现SO4-3-Gal糖共聚物在体外和体内都能抑制CD206，揭示了迄今为止未知的受体功能，并证明了它们在未来免疫治疗中作为CD206调节剂的潜力。
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.
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