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作 者:乐慧娟 吴瑾[1] LE Huijuan;WU Jin(Xinhua Hospital Affiliated to Shanghai Jiao Tong University of Medicine,Shanghai Institute for Pediatric Research,Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition,Shanghai 200092,China)
机构地区:[1]上海交通大学医学院附属新华医院、上海市儿科医学研究所、上海市小儿消化与营养重点实验室,上海200092
出 处:《临床儿科杂志》2025年第2期112-119,共8页Journal of Clinical Pediatrics
基 金:上海市自然科学基金(No.20ZR1446200)。
摘 要:目的 探讨坏死性小肠结肠炎(NEC)患儿外周血髓源性抑制细胞(MDSCs)数量变化与疾病进程的关系并分析患儿MDSCs的生物学特征。方法 下载GEO数据库NEC患儿外周血单个核细胞单细胞测序数据集并进行质控、批次矫正、降维聚类及细胞类群注释,计算MDSCs在NEC各期患儿外周血中的数量和比例;提取MDSCs亚群,分析各期NEC差异表达基因及富集通路;进一步比较MDSCs抑制功能、凋亡和趋化相关分子的表达变化情况。结果 随着NEC严重程度加重,相应的MDSCs细胞数量和比例逐渐降低。与Ⅱ期NEC患者相比,Ⅲ期NEC患者MDSCs中与白细胞激活正向调控、细胞运动负向调控等通路相关的基因显著上调;Ⅱ期和Ⅲ期NEC患者MDSCs的免疫抑制功能和凋亡通路活化情况无明显差异,但Ⅲ期NEC患者MDSCs中CXC基序趋化因子受体1(CXCR1)表达显著减少。结论 NEC患儿外周血MDSCs细胞数量与NEC严重程度负相关,Ⅲ期患儿外周血MDSCs细胞数量减少可能与其趋化因子受体CXCR1表达降低有关。Objective To investigate the correlation between peripheral blood myeloid-derived suppressor cells(MDSCs)levels and the severity of necrotizing enterocolitis(NEC),and the biological characteristics of MDSCs in NEC infants.Methods The single-cell sequencing dataset of peripheral blood from NEC patients was downloaded from the GEO database and analysed by quality control,batch correction,clustering dimensionality reduction and cell type annotation.The number and proportion of MDSCs in the peripheral blood of NEC patients at different disease stages were calculated.Subsequently,MDSCs subsets were extracted,differentially expressed genes and enrichment pathways were analysed,and the expression of MDSC immunosuppressive function,apoptosis and chemotaxis related molecules were compared.Results As the severity of NEC increased,the corresponding number and proportion of MDSCs gradually decreased.Compared with stage II NEC patients,upregulated genes in MDSCs of stage III NEC patients were enriched in multiple pathways,such as positive regulation of leukocyte activation and negative regulation of locomotion.And there was no significant difference in immunosuppressive function and apoptotic pathway activation between MDSCs from stage II and III NEC patients,whereas the expression of chemokine receptor CXCR1 was significantly decreased in MDSCs from stage III NEC patients.Conclusion The number of MDSCs in the peripheral blood of NEC patients was inversely correlated with the severity of NEC.And the reduction of MDSCs in stage III NEC patients could be attributed to the downregulated expression of CXCR1.
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