杀伤细胞凝集素样受体B1对类风湿关节炎外周血CD8^(+)T细胞功能的影响  

Effects of CD161 on peripheral blood CD8^(+)T cell function in patients with rheumatoid arthritis

作　　者：陆军勤 顾光学[1] 于洪威 周剑[2] LU Junqin;GU Guangxue;YU Hongwei;ZHOU Jian(Department of Trauma and Orthopedics,Lianyungang First People's Hospital,Lianyungang,Jiangsu 222000,China;Department of Orthopedics,The First Affiliated Hospital of Anhui Medical University,Hefei,Anhui 230032,China)

机构地区：[1]连云港市第一人民医院创伤骨科,江苏连云港222000 [2]安徽医科大学第一附属医院骨科,安徽合肥230032

出　　处：《安徽医药》2024年第11期2217-2221,I0008,共6页Anhui Medical and Pharmaceutical Journal

基　　金：安徽省自然科学基金项目(2208085MH212);连云港市第一人民医院青年英才基金项目(QN2304)。

摘　　要：目的研究杀伤细胞凝集素样受体B1(CD161)对类风湿关节炎(RA)病人外周血CD8^(+)T细胞及其亚群功能的影响。方法自2023年5―8月,整合基因组学数据库(GEO)不同数据集中对照组及RA组病人的外周血单细胞数据、Bulk转录组测序数据及临床相关数据,观察CD161在对照组及RA组中的表达差异情况。通过相关性分析指出CD161与RA病人临床炎症指标及治疗反应预后的相关性。运用单细胞无监督聚类、细胞注释方法观察CD161主要表达的细胞亚群及不同细胞亚群在对照组及RA组中的变化趋势。利用单细胞生物学评分功能计算不同亚群细胞的生物学功能评分,结合基因差异表达分析和功能富集分析,探索RA病人CD8^(+)T细胞及其亚群关键生物学功能与CD161基因表达的潜在关系。结果在人体外周全血中,与对照组相比,RA组中CD161高表达(8.779±0.657)(P<0.05),且CD161的表达与RA病人炎症因子C反应蛋白(CRP,r=−0.21)及血沉(ESR,r=−0.25)呈负相关(P<0.05)。CD161主要表达于NK细胞1.35±0.87、CD4^(+)T细胞0.62±0.82及CD8^(+)T细胞0.85±1.01,但在CD8^(+)T细胞中表达异质性最显著(标准差1.01大于平均数0.85),且CD161在CD8^(+)记忆T细胞中表达丰度最高1.38±0.34。与对照组相比,RA组中CD8^(+)T及CD8^(+)记忆T细胞频率均下降。与对照组相比,在RA病人外周血CD8^(+)记忆T细胞中,CD161表达降低(1.46±0.33比0.97±0.37,P<0.05),CD161与CD8^(+)记忆T细胞迁移(0.24±0.12比0.16±0.11)、细胞毒作用(0.52±0.27比0.45±0.38)呈正相关(均P<0.05),与趋化及促炎能力(0.15±0.04比0.17±0.02)呈负相关(P<0.05),与细胞增殖(0.02±0.04比0.03±0.04)或凋亡(0.12±0.22比0.18±0.18)相关性差异无统计学意义(P>0.05)。结论CD161介导CD8^(+)记忆T细胞细胞毒作用及促炎功能改变促进RA发生、发展。Objective To investigate the effect of killing cell lectin like receptor B1(CD161)on the function of peripheral blood CD8^(+)cells and their subsets in patients with rheumatoid arthritis(RA).Methods Peripheral blood single cell genomics data,bulk RNA-seq data,and clinical related data on the control and RA groups from May to August 2023 were integrated from different datasets of genomics database(GEO)database,and the differential expression of CD161 in the control and RA groups was observed.Through correlation analysis,the correlation between CD161 and clinical inflammatory indicators and treatment response prognosis in RA patients was identified.Single cell unsupervised clustering and cell annotation methods were used to observe the changes in the main and different cell subsets of CD161 expression in the control group and RA group.The biological function scores of different subsets of cells were calculated by using the single cell biological scoring function,combined with gene differential expression analysis and functional enrichment analysis,the potential relationship between the key biological functions of CD8^(+)T cells and their subsets and CD161 gene expression in RA patients was explored.Results In the peripheral whole blood of the human body,compared with the control group,CD161 was highly expressed in the RA group(8.779±0.657)(P<0.05),and the expression of CD161 was negatively correlated with the inflammatory factor C-reactive protein(CRP,r=−0.21)and erythrocyte sedimentation rate(ESR,r=−0.25)in RA patients(P<0.05).CD161 was mainly expressed in NK cells(1.35±0.87),CD4^(+)T cells 0.62±0.82,and CD8^(+)T cells 0.85±1.01,but the heterogeneity of expression was most significant in CD8^(+)T cells(standard deviation 1.01 greater than mean 0.85),and CD161 had the highest expression abundance in CD8^(+)memory T cells(1.38±0.34).Compared with the control group,the frequency of CD8^(+)T and CD8^(+)memory T cells decreased in the RA group,and CD161 expression was reduced in peripheral blood CD8^(+)memory

关 键 词：NK细胞凝集素样受体亚家族B CD8^(+)T细胞 记忆细胞 类风湿关节炎 

分 类 号：R593.22[医药卫生—内科学]