| First Author | Wang X | Year | 2022 |
| Journal | Cell Metab | Volume | 34 |
| Issue | 8 | Pages | 1088-1103.e6 |
| PubMed ID | 35921817 | Mgi Jnum | J:330795 |
| Mgi Id | MGI:7329658 | Doi | 10.1016/j.cmet.2022.07.005 |
| Citation | Wang X, et al. (2022) CD24-Siglec axis is an innate immune checkpoint against metaflammation and metabolic disorder. Cell Metab 34(8):1088-1103.e6 |
| abstractText | 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. |
