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CD24-Siglec信号轴是一种对抗代谢炎症和代谢紊乱的先天免疫检查点
作者:小柯机器人 发布时间:2022/8/5 16:11:44

CD24-Siglec信号轴是一种对抗代谢炎症和代谢紊乱的先天免疫检查点,这一成果由美国马里兰大学医学院Yang Liu、Pan Zheng等研究人员合作完成。该项研究成果发表在2022年8月2日出版的《细胞—代谢》杂志上。

由于CD24-Siglec相互作用调节对危险相关分子模式(DAMP)的炎症反应,研究人员产生了多个Cd24或Siglec基因单一或联合突变的小鼠品系,用于探索CD24-Siglec相互作用在代谢炎症和代谢紊乱中的作用。研究人员发现,CD24-Siglec-E信号轴,而不是其他Siglec,是肥胖相关代谢功能障碍的一个关键抑制因素。CD24-Siglec-E途径的失活加剧了饮食引起的代谢紊乱,包括肥胖、血脂异常、胰岛素抵抗和非酒精性脂肪性肝炎(NASH),而CD24Fc治疗则减轻了这种情况。
 
从机制上讲,Siglec-E对CD24的唾液酸化依赖性识别诱导SHP-1的招募并抑制代谢炎症,从而抵抗代谢综合征。一项关于CD24Fc(NCT02650895)的首次人体研究支持这一途径在人类脂质代谢和炎症中的重要性。这些发现确定了CD24-Siglec-E信号轴是对抗代谢炎症和代谢紊乱的先天免疫检查点,并提出了一个有希望的代谢性疾病的治疗靶标。
 
据介绍,调节代谢性疾病背后的慢性炎症的分子相互作用在很大程度上仍然未知。
 
附:英文原文
 
Title: CD24-Siglec axis is an innate immune checkpoint against metaflammation and metabolic disorder

Author: Xu Wang, Mingyue Liu, Jifeng Zhang, Nicholas K. Brown, Peng Zhang, Yan Zhang, Heng Liu, Xuexiang Du, Wei Wu, Martin Devenport, Weng Tao, Yang Mao-Draayer, Guo-Yun Chen, Y. Eugene Chen, Pan Zheng, Yang Liu

Issue&Volume: 2022/08/02

Abstract: The molecular interactions that regulate chronic inflammation underlying metabolic disease remain largely unknown. Since the CD24-Siglec interaction regulates inflammatory response to danger-associated molecular patterns (DAMPs), we have generated multiple mouse strains with single or combined mutations of Cd24 or Siglec genes to explore the role of the CD24-Siglec interaction in metaflammation and metabolic disorder. Here, we report that the CD24-Siglec-E axis, but not other Siglecs, is a key suppressor of obesity-related metabolic dysfunction. Inactivation of the CD24-Siglec-E pathway exacerbates, while CD24Fc treatment alleviates, diet-induced metabolic disorders, including obesity, dyslipidemia, insulin resistance, and nonalcoholic steatohepatitis (NASH). Mechanistically, sialylation-dependent recognition of CD24 by Siglec-E induces SHP-1 recruitment and represses metaflammation to protect against metabolic syndrome. A first-in-human study of CD24Fc (NCT02650895) supports the significance of this pathway in human lipid metabolism and inflammation. These findings identify the CD24-Siglec-E axis as an innate immune checkpoint against metaflammation and metabolic disorder and suggest a promising therapeutic target for metabolic disease.

DOI: 10.1016/j.cmet.2022.07.005

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(22)00304-7

期刊信息

Cell Metabolism:《细胞—代谢》,创刊于2005年。隶属于细胞出版社,最新IF:22.415
官方网址:https://www.cell.com/cell-metabolism/home
投稿链接:https://www.editorialmanager.com/cell-metabolism/default.aspx