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[高迁移率族蛋白B1(HMGB1)促进免疫性原发性血小板减少症患者髓样树突状细胞成熟并增加Th17细胞/Treg细胞比例]

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

作者信息

Li Qinzhi, Duan Dongsheng, Wang Xiujuan, Sun Mingling, Liu Ying, Wang Xinyou, Wang Lei, Fan Wenxia, Song Mengting, Guo Xinhong

机构信息

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.

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. *Corresponding author, E-mail:

出版信息

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2025 Jan;41(1):45-50.

Abstract

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 factor β(TGF-β). The mRNA levels of retinoic acid-related orphan receptor γt(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-β level 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.

摘要

目的 本研究探讨原发性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/调节性T细胞(Treg)平衡的调节作用。方法 本研究纳入30例新诊断的ITP患者及30例健康对照者。采用流式细胞术检测ITP患者和健康对照者外周血中mDC、Th17及Treg细胞的比例。采用酶联免疫吸附测定(ELISA)法检测血清HMGB1、白细胞介素6(IL-6)、IL-23、IL-17及转化生长因子β(TGF-β)水平。采用实时荧光定量聚合酶链反应(PCR)检测维甲酸相关孤儿受体γt(RORγt)和叉头框蛋白P3(FOXP3)的mRNA水平。采用Pearson线性相关分析评估上述细胞、细胞因子与血小板计数之间的相关性。结果 ITP患者外周血中Th17细胞比例、HMGB1、IL-6、IL-23、IL-17的表达水平及RORγt mRNA水平均高于健康对照者。然而,ITP患者Treg细胞比例及TGF-β水平低于健康对照者。ITP患者中,mDC比例及FOXP3 mRNA水平未显示出明显变化。mDC细胞比例与IL-6和IL-23的表达显著相关。此外,HMGB1的表达与mDC、IL-6、IL-23、RORγt mRNA及IL-17的表达显著相关。值得注意的是,mDC细胞比例及HMGB1的表达均与血小板计数呈负相关。结论 ITP患者外周血中HMGB1的高表达可能通过促进mDC成熟及影响细胞因子分泌诱导Th17/Treg失衡,从而可能在ITP的免疫机制中发挥作用。

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