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。

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