HMGB1在异基因造血干细胞移植后急性移植物抗宿主病患者CD4(+) T细胞中STAT3表达调控中的作用
Role of HMGB1 in regulation of STAT3 expression in CD4(+) T cells from patients with aGVHD after allogeneic hematopoietic stem cell transplantation.
作者信息
Xu Ya-Jing, Li Lin, Chen Yan, Fu Bin, Wu Deng-Shu, Li Xiao-Lin, Zhao Xie-Lan, Chen Fang-Ping
机构信息
Department of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Department of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
出版信息
Clin Immunol. 2015 Dec;161(2):278-83. doi: 10.1016/j.clim.2015.08.012. Epub 2015 Aug 29.
Treg/Th17 balance plays a critical role in maintaining immune homeostasis of acute graft-versus-host disease (aGVHD) patients. STAT3 is an important factor involved in the instability of Treg and the promotion of Th17. HMGB1 is a cytokine mediator of inflammation and an important chromatin protein regulating gene transcription. In this study, we found that the expressions of HMGB1 and STAT3 were higher in CD4(+) T cells of patients with aGVHD compared with those without aGVHD, and the HMGB1 expression was positively correlated with the STAT3 expression. Simultaneously, their expressions were positively correlated with the severity of the aGVHD. We also demonstrated that HMGB1 could regulate the expression of STAT3 by modulation of its DNA methylation in CD4(+) T cells, moreover downregulated HMGB1 in aGVHD CD4(+) T cells could change the ratio of Treg/Th17. These data strongly suggest that HMGB1 plays a crucial role in the regulation of Treg/Th17 and progression of aGVHD.
调节性T细胞/辅助性T细胞17（Treg/Th17）平衡在维持急性移植物抗宿主病（aGVHD）患者的免疫稳态中起关键作用。信号转导和转录激活因子3（STAT3）是参与调节性T细胞（Treg）不稳定和辅助性T细胞17（Th17）增殖的重要因素。高迁移率族蛋白B1（HMGB1）是一种炎症细胞因子介质，也是一种调节基因转录的重要染色质蛋白。在本研究中，我们发现与未患aGVHD的患者相比，aGVHD患者的CD4(+) T细胞中HMGB1和STAT3的表达更高，且HMGB1表达与STAT3表达呈正相关。同时，它们的表达与aGVHD的严重程度呈正相关。我们还证明，HMGB1可通过调节CD4(+) T细胞中STAT3的DNA甲基化来调控其表达，此外，下调aGVHD CD4(+) T细胞中的HMGB1可改变Treg/Th17的比例。这些数据有力地表明，HMGB1在调节Treg/Th17和aGVHD进展中起关键作用。
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