CD177 + neutrophils drive extracellular matrix remodelling and HGF-alpha release in ALPPS-induced liver regeneration

作者：Jiayan Yan, Ao Huang, Shiyu Zhang, Na Yao, Junfeng Huang, Zhifeng Jiang, Jia‐Yi Wang, Feiyu Chen, Qichao Yu, Jian‐Wen Cheng, Senquan Zhang, Tianyi Li, Rong Gao, Runze Miao, Rongkui Luo, Shao‐Lai Zhou, Yuan Ji, Zheng Wang, Dongmei Gao, Zhen‐Bin Ding, Zhao–You Tang, Jia Fan, Miguel A. Esteban, Hans J. Schlitt, Xin‐Rong Yang, Jian Zhou · 发表于：Gut · 年份：2025 · DOI：10.1136/gutjnl-2025-336300 · 被引用次数：4 · 研究领域：Liver physiology and pathology、Neutrophil, Myeloperoxidase and Oxidative Mechanisms、Cell Adhesion Molecules Research

Background Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) effectively induces rapid liver hypertrophy in patients with initially unresectable liver tumours, yet the immunological mechanisms remain unclear. Objective We aim to elucidate the immune alterations and underlying mechanisms driving liver regeneration following ALPPS. Design The cohort study included single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics on remnant liver tissues from ALPPS patients. Neutrophil infiltration was validated by flow cytometry and histological analyses in the world’s largest ALPPS clinical cohort and mouse ALPPS models. Functional validation, including neutrophil depletion, matrix metalloproteinase 9 (MMP9) inhibition and CD177 blockade, as well as Cd177 knockout and CD177 + neutrophil infusion in vivo. Results scRNA-seq revealed substantial neutrophil infiltration following stage 1 ALPPS. Depletion of neutrophils impaired liver regeneration. Among subsets, CD177 + neutrophils were metabolically active with enhanced neutrophil extracellular traps formation and secreted MMP9. MMP9 inhibition disrupted extracellular matrix (ECM) degradation and hepatocyte growth factor alpha (HGF-α) release, impairing regeneration. CD177 + neutrophils interacted with endothelial cells via CD177–PECAM1 to facilitate transmigration, while hepatic stellate cell-derived CXCL8 promoted neutrophil chemotaxis via CXCL8–CXCR1/2. Cd177 deficiency attenuated neutrophil ...