高迁移率族蛋白B1(HMGB1)促进髓样树突状细胞成熟增加原发免疫性血小板减少症患者Th17细胞/Treg比例  

High mobility group protein B1(HMGB1)promotes myeloid dendritic cell maturation and increases Th17 cell/Treg cell ratio in patients with immune primary thrombocytopenia

作　　者：李芹芝 段东升 王秀娟[1] 孙明玲[1] 刘颖[1] 王新有[1] 王蕾[1] 范文霞 宋梦婷 郭新红[1] LI Qinzhi;DUAN Dongsheng;WANG Xiujuan;SUN Mingling;LIU Ying;WANG Xinyou;WANG Lei;FAN Wenxia;SONG Mengting;GUO Xinhong(Hematologic Disease Center,First Affiliated Hospital of Xinjiang Medical University,Xinjiang Uygur Autonomous Region Research Institute of Hematology,Xinjiang Medical University,Urumqi,Xinjiang Uygur Autonomous Region,Wulumuqi 830011,China)

机构地区：[1]新疆医科大学第一附属医院血液病中心,新疆维吾尔自治区血液病研究所,新疆血液病临床医学研究中心,新疆乌鲁木齐830011

出　　处：《细胞与分子免疫学杂志》2025年第1期45-50,共6页Chinese Journal of Cellular and Molecular Immunology

基　　金：国家自然科学基金(82160032)。

摘　　要：目的研究原发免疫性血小板减少症(ITP)患者外周血中高迁移率族蛋白B1(HMGB1)对髓样树突状细胞(mDC)及Th17细胞/调节性T细胞(Treg)平衡的调节作用。方法募集30例初诊ITP患者及30例健康对照,采用流式细胞术检测ITP患者及健康对照组外周血mDC、Th17细胞、Treg比例,ELISA测定血清中HMGB1、白细胞介素6(IL-6)、IL-23、IL-17、转化生长因子β(TGF-β)的含量,实时荧光定量PCR检测外周血单个核细胞维甲酸相关孤核受体γt(RORγt)、叉头盒转录因子P3(FOXP3)的mRNA表达,通过Pearson线性相关分析方法分析上述细胞、细胞因子、转录因子及其与血小板之间的相关关系,探究HMGB1对mDC及Th17细胞/Treg平衡的影响。结果与对照组相比,ITP患者组外周血中Th17细胞比例及HMGB1、IL-6、IL-23、IL-17水平及RORγt mRNA表达明显增高,而Treg比例和TGF-β水平降低。ITP患者组mDC比例和FOXP3 mRNA水平变化不明显。mDC的比例与IL-6、IL-23的表达显著正相关;HMGB1的表达与mDC、IL-6、IL-23、RORγt mRNA、IL-17的表达显著正相关;mDC的比例、HMGB1的表达水平与血小板计数呈显著负相关。结论ITP患者外周血中HMGB1的高表达可能通过促进mDC的成熟并增加相关细胞因子的分泌,诱导Th17细胞/Treg失衡,可能参与ITP发病的免疫学机制。Objective This study investigated the regulatory effect of high mobility group protein B1(HMGB1)in the peripheral blood of patients with primary immune thrombocytopenia(ITP)on myeloid dendritic cells(mDC)and Th17/regulatory T cells(Treg)balance.Methods The study enrolled 30 newly diagnosed ITP patients and 30 healthy controls.Flow cytometry was used to measure the proportion of mDC,Th17,and Treg cells in the peripheral blood of ITP patients and healthy controls.ELISA was conducted to quantify the serum levels of HMGB1,interleukin 6(IL-6),IL-23,IL-17,and transforming growth factorβ(TGF-β).The mRNA levels of retinoic acid-related orphan receptorγt(RORγt)and forehead box P3(FOXP3)were detected by real-time PCR.The correlation between the abovementioned cells,cytokines,and platelet count was assessed using Pearson linear correlation analysis.Results The proportion of Th17 cells and the expression levels of HMGB1,IL-6,IL-23,IL-17 and the level of RORγt mRNA in the peripheral blood of ITP patients were higher than those in healthy controls.However,the Treg cell proportion and TGF-βlevel were lower in ITP patients than those in healthy controls.In patients with ITP,the proportion of mDC and the level of FOXP3 mRNA did not show significant changes.The proportion of mDC cells was significantly correlated with the expression of IL-6 and IL-23.Moreover,the expression of HMGB1 showed a significant correlation with the expression of mDC,IL-6,IL-23,RORγt mRNA,and IL-17.Notably,both the proportion of mDC cells and the expression of HMGB1 were negatively correlated with platelet count.Conclusion The high expression of HMGB1 in peripheral blood of ITP patients may induce Th17/Treg imbalance by promoting the maturation of mDC and affecting the secretion of cytokines,thereby potentially playing a role in the immunological mechanism of ITP.

关 键 词：原发免疫性血小板减少症 高迁移率族蛋白B1(HMGB1) 髓样树突状细胞(mDC) TH17细胞 TREG 

分 类 号：R392[医药卫生—免疫学] R558.2[医药卫生—基础医学] R392.12