α-Ketoglutarate alleviates the pathogenesis of lupus and inhibits the activation and differentiation of B cells by promoting the expression of CD39

• DOI: 10.1007/s00018-025-05734-5
• Publication Date: 2025-05-28T03:32:15Z
• Authors: Yangzhe Gao; Yucai Xiao; Yuxin Hu; Lu Yu; Jiakun Liu; Zhengyi Zhang; Tianqi Zhao; Shuo Zhao; Lili Zhang; Yonghong Yang; Huabao Xiong; Guanjun Dong
• Keywords: Pathogenesis

The abnormal activation and differentiation of B cells play an important role in the pathogenesis autoimmune diseases, including systemic lupus erythematosus (SLE). Alpha-ketoglutarate (α-KG), a key metabolite tricarboxylic acid cycle, has been shown to be involved many diseases by regulating immune response. However, α-KG SLE, as well cells, remains unclear. In this study, we used organic acid-targeted metabolomics analyze changes levels 100 acids serum SLE patients healthy controls, found significant increase level compared that controls. Notably, significantly could inhibit alleviate disease progression lupus-prone mice. Mechanistically, RNA-seq revealed upregulated expression ENTPD1, which encodes checkpoint molecule CD39; B-cell-specific loss ENTPD1 promote Toll-like receptors-mediated aggravate conditions findings our study demonstrate alleviates inhibits increasing CD39. Our laid theoretical foundation for understanding SLE. Based on might further examined drug effective treatment