摘要
目的:揭示肾移植受者术后发生抗体介导排斥反应(antibody-mediated rejection,ABMR)的潜在机制。方法:选取肾移植术后6个月以上的受者作为研究对象,利用单细胞RNA测序(single-cell RNA sequencing,scRNA-seq)技术,对受者外周血单个核细胞(peripheral blood mononuclear cell,PBMC)中的免疫细胞亚群展开高分辨率的scRNA-seq分析。采用流式细胞技术检测不同免疫细胞群中差异基因对ABMR的影响。结果:本研究通过单细胞测序技术分析了ABMR受者与正常对照组的差异基因表达,发现CD69、CD83、CD52、CD74和CX3CR1为主要的差异基因。在经典单核细胞中,ABMR受者的CD83和CD52基因表达量较正常组有所增加,而治疗后呈现降低趋势;在初始CD4+T细胞中,ABMR受者的CD69基因表达量较正常组显著下降;在NK细胞中,ABMR受者的CX3CR1基因表达量较正常组降低,而治疗后CX3CR1的几何平均值进一步降低,CD74的几何平均值则有增加趋势。结论:经典单核细胞中CD83和CD52基因表达上调,与抗原提呈细胞的功能增强相关,从而促进ABMR的发生。初始CD4+T细胞中CD69基因表达上调,与T细胞的激活和增殖相关,进一步参与ABMR的进程。相反,NK细胞中CX3CR1基因表达下调,与NK细胞的免疫监视功能障碍相关,从而在一定程度上抑制ABMR的发生。
AIM:Based on single-cell sequencing analysis,the underlying mechanism of antibodymediated rejection(ABMR)in kidney transplant recipients.METHODS:Recipients with 6 months or more after kidney transplantation were selected as research subjects,and high-resolution scRNA-seq analysis of immune cell subsets in peripheral blood mononuclear cells(PBMC)was performed using single-cell RNA sequencing(scRNA-seq)technology.Flow cytometry was used to examine the effect of differential genes on renal transplant ABMR in different immune cell populations.RESULTS:This study analyzed differential gene expression between ABMR patients and healthy controls using single-cell sequencing technology,identifying CD69,CD83,CD52,CD74,and CX3CR1 as key differentially expressed genes.In classical monocytes,ABMR patients exhibited increased CD83 and CD52 gene expression levels compared to the control group,which showed a downward trend after treatment.Regarding initial CD4+T cells,ABMR patients demonstrated significantly reduced CD69 gene expression.In NK cells,ABMR patients displayed decreased CX3CR1 gene expression initially,with further reduction in its geometric mean value post-treatment.Conversely,the geometric mean value of CD74 showed an increasing trend.CONCLUSION:In classical mononuclear cells,upregulated expression of CD83 and CD52 genes correlates with enhanced antigen-presenting cell functionality,thereby promoting the development of antigen-bonded microenvironment remodeling(ABMR).In initial CD4+T cells,elevated CD69 gene expression is associated with T cell activation and proliferation,further contributing to ABMR progression.Conversely,downregulated CX3CR1 gene expression in NK cells relates to impaired immune surveillance mechanisms,which partially inhibits ABMR formation.
作者
郑凯乐
付嘉钊
尤佳
吴丹
王学彬
王卓
ZHENG Kaile;FU Jiazhao;YOU Jia;WU Dan;WANG Xuebin;WANG Zhuo(School of Pharmacy,Bengbu Medical College,Bengbu 233030,Anhui,China;Department of Pharmacy,Shanghai Children's Hospital,Shanghai 200062,China;Department of Pharmacy,the First Affiliated Hospital of Naval Medical University,Shanghai 200433,China;Department of Organ Transplantation,the First Affiliated Hospital of Naval Medical University,Shanghai 200433,China;Bioinformatics Center of Shanghai Children's Hospital,Shanghai 200062,China)
出处
《中国临床药理学与治疗学》
北大核心
2026年第3期289-299,共11页
Chinese Journal of Clinical Pharmacology and Therapeutics
基金
国家自然科学基金资助项目(82173900)
促进市级医院临床技能与临床创新能力三年行动计划(SHDC2020CR4072)
2022年上海青年药学人才能力提升项目(沪药会字[2023]04号)
上海市儿童医院人才引进启动项目(SHSERTYY20250505)。
