Recombinant HMGB1 A box protein inhibits Th17 responses in mice with neutrophilic asthma by suppressing dendritic cell-mediated Th17 polarization
Recombinant HMGB1 A box protein inhibits Th17 responses in mice with neutrophilic asthma by suppressing dendritic cell-mediated Th17 polarization
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重组 HMGB1 A box 蛋白通过抑制树突状细胞介导的 Th17 极化来抑制中性粒细胞性哮喘小鼠的 Th17 反应
DOI：
10.1016/j.intimp.2014.11.005
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发表时间：
2015-01-01
影响因子：
5.6
通讯作者：
Song, Yong
中科院分区：
文献类型：
--
作者：
Zhang, Fang;Huang, Gang;Song, Yong
高迁移率族蛋白1（HMGB 1）是一种重要的促炎细胞因子，参与多种炎症性疾病，对过敏性哮喘具有重要的免疫调节作用。我们最近的研究表明，在嗜肺性哮喘小鼠模型中，HMGB 1）（Lambda）Adfigure = Yes 1在肺组织中表达增加，并与白细胞介素-17（+）（IL-17）辅助性T细胞（Th 17）应答相关。在这项研究中，我们研究了HMGB 1的免疫调节机制，评估了重组HMGB 1 A盒（HMGB 1的拮抗剂）的管理对过敏性气道炎症和肺抗原呈递细胞（APC）功能的影响在小鼠哮喘模型。在OVA攻击的小鼠中，rHMGB 1 A盒减弱HMGB 1表达、气道嗜酸性炎症和高反应性。此外，rHMGB 1 A box还能降低肺细胞中Th 17细胞和IL-23（+）CD 11 c（+）APC的数量。在体内，rHMGB 1 A box揭示了rHMGB 1激活的树突状细胞（DC）产生IL-23和诱导Th 17应答的抑制作用。最后，我们发现过继转移rHMGB 1激活的DC足以恢复DC驱动的哮喘模型中的嗜肺性哮喘的特征，而转移rHMGB 1 A盒加rHMGB 1激活的DC显著降低这些炎症表型。这些数据表明，rHMGB 1 A box可能通过阻断DCs上的HMGB 1通路而对嗜肺性哮喘的Th 17极化和气道炎症具有治疗作用。(C)2014爱思唯尔有限公司版权所有。
High mobility group box chromosomal protein 1 (HMGB1) is a critical pro-inflammatory cytokine involved in diverse inflammatory diseases and has important immunomodulatory effects on allergic asthma. Our recent studies demonstrate that HMGB1) (Lambda)ReloadFigure=Yes1 expression increases in the lung tissue and associates with interleukin-17(+) (IL-17) helper T cell (Th17) responses in a murine model of neutrophilic asthma. In this study, to examine the immunomodulatory mechanisms of HMGB1, we evaluated the effects of recombinant HMGB1 A box (an antagonist of HMGB1) administration on allergic airway inflammation and lung antigen-presenting cell (APC) function in a murine model of neutrophilic asthma. In OVA-challenged mice, rHMGB1 A box attenuated HMGB1 expression, airway neutrophilic inflammation and hyper-responsiveness. In addition, the administration of rHMGB1 A box decreased the number of Th17 cells and IL-23(+) CD11c(+) APCs in lung cells. In vivo, rHMGB1 A box revealed an inhibitory effect of rHMGB1-activated dendritic cells (DCs) to produce IL-23 and induce a Th17 response. Finally, we showed that adoptive transfer of rHMGB1-activated DCs was sufficient to restore the characteristics of neutrophilic asthma in a DCs-driven model of asthma, whereas the transfer of rHMGB1 A box plus rHMGB1-activated DCs significantly reduced these inflammation phenotypes. These data demonstrate that rHMGB1 A box may have therapeutic effects on controlling Th17 polarization and airway inflammation in neutrophilic asthma by blocking the HMGB1 pathway on DCs. (C) 2014 Elsevier B.V. All rights reserved.