Enhancing regulatory T-cell function via inhibition of high mobility group box 1 protein signaling in immune thrombocytopenia.
Enhancing regulatory T-cell function via inhibition of high mobility group box 1 protein signaling in immune thrombocytopenia.
复制标题
通过抑制免疫性血小板减少症中的高迁移率族蛋白 1 蛋白信号传导增强调节性 T 细胞功能
DOI：
10.3324/haematol.2022.281557
复制
发表时间：
2023-03-01
期刊：
影响因子：
10.1
通讯作者：
Hou, Yu
中科院分区：
文献类型：
--
作者：
Wang, Haoyi;Yu, Tianshu;An, Ning;Sun, Yunqi;Xu, Pengcheng;Han, Panpan;Zhao, Yajing;Wang, Lingjun;Ni, Xiaofei;Li, Yubin;Li, Guosheng;Liu, Yanfeng;Peng, Jun;Hou, Ming;Hou, Yu
原发性免疫性血小板减少症（ITP）是最常见的获得性自身免疫性出血性疾病。高迁移率组框1 （HMGB1）蛋白异常升高与血小板减少症和ITP治疗结果相关先前的研究表明，HMGB1的一种天然抑制剂18β-甘草酸（18β-GA）可能具有抗炎和免疫调节作用，但其在ITP中纠正免疫平衡的能力尚不清楚。在本研究中，我们发现ITP患者血浆HMGB1与血小板计数呈负相关，并证实18β-GA通过阻断ITP患者HMGB1对HMGB1的影响，刺激调节性T细胞（regulatory T cells, Treg）的产生，恢复CD4+ T细胞亚群的平衡，增强Treg的抑制功能。HMGB1短发夹RNA干扰掩盖了18β-GA在ITP患者Treg中的作用。此外，我们发现18β-GA可减轻ITP小鼠的血小板减少症。简单地说，将抗cd61免疫致敏的脾细胞转移到严重联合免疫缺陷小鼠体内，以诱导严重ITP小鼠模型。经18β-GA处理后，ITP小鼠循环Treg比例显著升高，血浆HMGB1水平和血清抗血小板抗体水平显著降低。此外，在ITP患者和ITP小鼠中，18β-GA均可降低巨噬细胞对血小板的吞噬活性。这些结果表明，18β-GA可能通过抑制HMGB1信号通路来恢复ITP的免疫平衡。总之，本研究揭示了HMGB1在ITP中的作用，它可能作为血小板减少治疗的潜在靶点。
Primary immune thrombocytopenia (ITP) is the most common acquired autoimmune bleeding disorder. Abnormally increased levels of High Mobility Group Box 1 (HMGB1) protein associate with thrombocytopenia and therapeutic outcome in ITP. Previous studies proposed that a natural inhibitor of HMGB1, 18β-glycyrrhetinic acid (18β-GA), could be used for its anti-inflammatory and immune-modulatory effects, although its ability to correct immune balance in ITP is unclear. In this study, we showed that plasma HMGB1 correlated negatively with platelet counts in ITP patients, and confirmed that 18β-GA stimulated the production of regulatory T cells (Treg), restored the balance of CD4+ T-cell subsets and enhanced the suppressive function of Treg through blocking the effect on HMGB1 in patients with ITP. HMGB1 short hairpin RNA interference masked the effect of 18β-GA in Treg of ITP patients. Furthermore, we found that 18β-GA alleviated thrombocytopenia in mice with ITP. Briefly, anti-CD61 immune-sensitized splenocytes were transferred into severe combined immunodeficient mice to induce a murine model of severe ITP. The proportion of circulating Treg increased significantly, while the level of plasma HMGB1 and serum antiplatelet antibodies decreased significantly in ITP mice along 18β-GA treatment. In addition, 18β-GA reduced phagocytic activity of macrophages towards platelets both in ITP patients and ITP mice. These results indicate that 18β-GA has the potential to restore immune balance in ITP via inhibition of HMGB1 signaling. In short, this study reveals the role of HMGB1 in ITP, which may serve as a potential target for thrombocytopenia therapy.
登录
查看更多内容
高迁移率组Box-1蛋白1中的Toll样受体4信号传导介导了调节T细胞的抑制。
DOI：
10.12659/msm.902081
发表时间：
2017-01-18
期刊：
Medical science monitor : international medical journal of experimental and clinical research
影响因子：
--
作者：
Luo C;Liu H;Wang H;Wang J
通讯作者：
Wang J
影响因子：
3.8
作者：
Kawashima, Daisuke;Asai, Midori;Ohtsuka, Kenzo
通讯作者：
Ohtsuka, Kenzo
影响因子：
3.6
作者：
Li, Ruiting;Wang, Jing;Yang, Jiong
通讯作者：
Yang, Jiong
影响因子：
20.3
作者：
Liu, Xin-guang;Ma, Shi-hui;Peng, Jun
通讯作者：
Peng, Jun
影响因子：
4.8
作者：
Evankovich, John;Cho, Sung W.;Tsung, Allan
通讯作者：
Tsung, Allan