Guangdong Provincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, China.
Clinical Laboratory, Guangzhou Red Cross Hospital, Jinan University, Guangzhou 510220, China.
Clin Immunol. 2024 Nov;268:110355. doi: 10.1016/j.clim.2024.110355. Epub 2024 Sep 3.
Biliary atresia (BA) is a severe pediatric liver disease characterized by progressive bile duct destruction and fibrosis, leading to significant liver damage and frequently necessitating liver transplantation. This study elucidates the role of LOX-1 polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in BA pathogenesis and assesses their potential as non-invasive early diagnostic biomarkers. Using flow cytometry, immunofluorescence, and molecular profiling, we analyzed the expression and activity of these cells in peripheral blood and liver tissues from BA patients and controls. Our findings reveal a significant increase in the frequencies and function of LOX-1PMN-MDSCs in BA patients, along with MAPK signaling pathway upregulation, indicating their involvement in disease mechanisms. Additionally, the frequencies of LOX-1PMN-MDSC in peripheral blood significantly positively correlate with liver function parameters in BA patients, demonstrating diagnostic performance comparable to traditional serum markers. These findings suggest that LOX-1PMN-MDSCs contribute to the immunosuppressive environment in BA and could serve as potential diagnostic targets.
先天性胆道闭锁(BA)是一种严重的儿科肝脏疾病,其特征为进行性胆管破坏和纤维化,导致显著的肝损伤,并经常需要进行肝移植。本研究阐明了 LOX-1 多形核髓系来源的抑制细胞(PMN-MDSCs)在 BA 发病机制中的作用,并评估了它们作为非侵入性早期诊断生物标志物的潜力。我们使用流式细胞术、免疫荧光和分子谱分析,分析了 BA 患者和对照组外周血和肝组织中这些细胞的表达和活性。我们的研究结果表明,BA 患者中 LOX-1PMN-MDSCs 的频率和功能显著增加,同时 MAPK 信号通路上调,表明它们参与了疾病机制。此外,外周血中 LOX-1PMN-MDSC 的频率与 BA 患者的肝功能参数显著正相关,表明其诊断性能可与传统的血清标志物相媲美。这些发现表明,LOX-1PMN-MDSCs 有助于 BA 中的免疫抑制环境,并且可能成为潜在的诊断靶标。