{"title":"MAPK 信号通路在胆道闭锁中诱导 LOX-1+ 多形核髓鞘源性抑制细胞。","authors":"","doi":"10.1016/j.clim.2024.110355","DOIUrl":null,"url":null,"abstract":"<div><p>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<sup>+</sup> 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-1<sup>+</sup>PMN-MDSCs in BA patients, along with MAPK signaling pathway upregulation, indicating their involvement in disease mechanisms. Additionally, the frequencies of LOX-1<sup>+</sup>PMN-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-1<sup>+</sup>PMN-MDSCs contribute to the immunosuppressive environment in BA and could serve as potential diagnostic targets.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":null,"pages":null},"PeriodicalIF":4.5000,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"MAPK signaling pathway induced LOX-1+ polymorphonuclear myeloid-derived suppressor cells in biliary atresia\",\"authors\":\"\",\"doi\":\"10.1016/j.clim.2024.110355\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>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<sup>+</sup> 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-1<sup>+</sup>PMN-MDSCs in BA patients, along with MAPK signaling pathway upregulation, indicating their involvement in disease mechanisms. Additionally, the frequencies of LOX-1<sup>+</sup>PMN-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-1<sup>+</sup>PMN-MDSCs contribute to the immunosuppressive environment in BA and could serve as potential diagnostic targets.</p></div>\",\"PeriodicalId\":10392,\"journal\":{\"name\":\"Clinical immunology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.5000,\"publicationDate\":\"2024-09-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1521661624004649\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical immunology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1521661624004649","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
胆道闭锁(BA)是一种严重的小儿肝病,其特点是进行性胆管破坏和纤维化,导致严重的肝损伤,经常需要进行肝移植。本研究阐明了LOX-1+多形核髓源性抑制细胞(PMN-MDSCs)在胆道闭锁发病机制中的作用,并评估了它们作为非侵入性早期诊断生物标志物的潜力。我们利用流式细胞术、免疫荧光和分子图谱分析了这些细胞在 BA 患者和对照组的外周血和肝组织中的表达和活性。我们的研究结果表明,在 BA 患者中,LOX-1+PMN-MDSCs 的频率和功能明显增加,同时 MAPK 信号通路上调,这表明它们参与了疾病机制。此外,外周血中 LOX-1+PMN-MDSC 的频率与 BA 患者的肝功能指标呈显著正相关,其诊断性能与传统的血清标志物相当。这些研究结果表明,LOX-1+PMN-MDSCs 对 BA 的免疫抑制环境做出了贡献,可作为潜在的诊断目标。
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-1+PMN-MDSCs in BA patients, along with MAPK signaling pathway upregulation, indicating their involvement in disease mechanisms. Additionally, the frequencies of LOX-1+PMN-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-1+PMN-MDSCs contribute to the immunosuppressive environment in BA and could serve as potential diagnostic targets.
期刊介绍:
Clinical Immunology publishes original research delving into the molecular and cellular foundations of immunological diseases. Additionally, the journal includes reviews covering timely subjects in basic immunology, along with case reports and letters to the editor.