Atg5 deficiency in basophils improves metabolism in lupus mice by regulating gut microbiota dysbiosis

作者：Jiaxuan Chen, Quanren Pan, Quanren Pan, Lu Lu, Xiaorong Huang, Shuting Wang, Xiaoxian Liu, Jiaqi Lun, Hong-yong Su, Hongyong Su, Fengbiao Guo, Lawei Yang, Liuyong You, Haiyan Xiao, Wenying Luo, Hua-feng Liu, Qingjun Pan, Qingjun Pan · 发表于：Cell Communication and Signaling · 年份：2025 · DOI：10.1186/s12964-025-02041-1 · 被引用次数：15 · 研究领域：Immune Cell Function and Interaction、Gut microbiota and health、Helicobacter pylori-related gastroenterology studies

Autophagic activation in immune cells, gut microbiota dysbiosis, and metabolic abnormalities have been reported separately as characteristics of systemic lupus erythematosus (SLE). Elucidating the crosstalk among the immune system, commensal microbiota, and metabolites is crucial to understanding the pathogenesis of autoimmune diseases. Emerging evidence shows that basophil activation plays a critical role in the pathogenesis of SLE; however, the underlying mechanisms remain largely unknown. Here, we investigated the effects of autophagic inhibition on the pathogenesis of basophils in SLE using Autophagy-related gene 5 (Atg5) knockout ( Atg5 −/− ) as an autophagic inhibitor. Specifically, we knocked out basophilic Atg5 in vivo to investigate its impact on lupus metabolism. Furthermore, Atg5 −/− basophils were transferred to basophil-depleted MRL/MpJ- Fas lpr (MRL/ lpr ) mice to study their effect on disease metabolism. Metagenomic and targeted metabolomic sequencing results indicated considerable reduction in the levels of plasma autoantibodies and inflammatory cytokines in the Atg5 −/− basophil transfer group compared with that in the control group. Transplanting Atg5 −/− basophils improved the gut microbiota balance in MRL /lpr mice, increasing the abundance of beneficial bacteria, such as Ligilactobacillus murinus and Faecalitalea rodentium , and reducing that of potentially pathogenic bacteria such as Phocaeicola salanitronis . The transplantation of Atg5 -deficient basop...