首页|期刊导航|中国临床药理学与治疗学|单细胞测序揭示肾移植受者抗体介导排斥反应的潜在机制

单细胞测序揭示肾移植受者抗体介导排斥反应的潜在机制OA

Single-cell sequencing reveals the underlying mechanism of antibody-mediated rejection in renal transplant recipients

中文摘要英文摘要

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 antibody-mediated rejection(ABMR)in kidney transplant re-cipients.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 sin-gle-cell RNA sequencing(scRNA-seq)technology.Flow cytometry was used to examine the effect of differential genes on renal transplant ABMR in dif-ferent immune cell populations.RESULTS:This study analyzed differential gene expression be-tween 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 pa-tients exhibited increased CD83 and CD52 gene ex-pression levels compared to the control group,which showed a downward trend after treatment.Regarding initial CD4+T cells,ABMR patients demon-strated significantly reduced CD69 gene expression.In NK cells,ABMR patients displayed decreased CX3CR1 gene expression initially,with further re-duction in its geometric mean value post-treat-ment.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 pro-moting the development of antigen-bonded mi-croenvironment remodeling(ABMR).In initial CD4+T cells,elevated CD69 gene expression is associated with T cell activation and proliferation,further con-tributing to ABMR progression.Conversely,down-regulated CX3CR1 gene expression in NK cells re-lates to impaired immune surveillance mechanisms,which partially inhibits ABMR formation.

郑凯乐;付嘉钊;尤佳;吴丹;王学彬;王卓

蚌埠医科大学药学院,蚌埠 233030,安徽||上海市儿童医院药学部,上海 200062||海军军医大学第一附属医院药剂科,上海 200433海军军医大学第一附属医院器官移植科,上海 200433蚌埠医科大学药学院,蚌埠 233030,安徽||上海市儿童医院药学部,上海 200062||海军军医大学第一附属医院药剂科,上海 200433上海市儿童医院生物信息学中心,上海 200062上海市儿童医院药学部,上海 200062||海军军医大学第一附属医院药剂科,上海 200433海军军医大学第一附属医院药剂科,上海 200433

医药卫生

他克莫司肾移植排斥反应差异基因PBMC

tacrolimuskidney transplantationrejectiondifferential genePBMC

《中国临床药理学与治疗学》 2026 (3)

289-299,11

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)

10.12092/j.issn.1009-2501.2026.03.001

评论