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RAGE-induced ILC2 expansion in acute lung injury due to haemorrhagic shock.

出血休克引起的急性肺损伤中 RAGE 诱导的 ILC2 扩张。

  • 影响因子:4.63
  • DOI:10.1136/thoraxjnl-2019-213613
  • 作者列表:"Zhang K","Jin Y","Lai D","Wang J","Wang Y","Wu X","Scott M","Li Y","Hou J","Billiar T","Wilson M","Shu Q","Fang X","Fan J
  • 发表时间:2020-01-14
Abstract

BACKGROUND:Type 2 immune dysfunction contributes to acute lung injury and lethality following haemorrhagic shock (HS) and trauma. Group 2 innate lymphoid cells (ILC2s) play a significant role in the regulation of type 2 immune responses. However, the role of ILC2 in post-HS acute lung injury and the underlying mechanism has not yet been elucidated. OBJECTIVE:To investigate the regulatory role of ILC2s in HS-induced acute lung injury and the underlying mechanism in patients and animal model. METHODS:Circulating markers of type 2 immune responses in patients with HS and healthy controls were characterised. Using a murine model of HS, the role of high-mobility group box 1 (HMGB1)-receptor for advanced glycation end products (RAGE) signalling in regulation of ILC2 proliferation, survival and function was determined. And the role of ILC2 in inducing type 2 immune dysfunction was assessed as well. RESULTS:The number of ILC2s was significantly increased in the circulation of patients with HS that was correlated with the increase in the markers of type 2 immune responses in the patients. Animal studies showed that HMGB1 acted via RAGE to induce ILC2 accumulation in the lungs by promoting ILC2 proliferation and decreasing ILC2 death. The expansion of ILC2s resulted in type 2 cytokines secretion and eosinophil infiltration in the lungs, both of which contributed to lung injury after HS. CONCLUSIONS:These results indicate that HMGB1-RAGE signalling plays a critical role in regulating ILC2 biological function that aggravates type 2 lung inflammation following HS.

摘要

背景: 2 型免疫功能紊乱导致失血性休克和创伤后的急性肺损伤和致死。第 2 组固有淋巴细胞 (ILC2s) 在调节 2 型免疫反应中起着重要作用。然而,ILC2 在 HS 后急性肺损伤中的作用及其机制尚未阐明。 目的: 探讨 ILC2s 在急性肺损伤中的调节作用及其机制。 方法: 对 HS 患者和健康对照者的循环 2 型免疫反应标志物进行表征。使用 HS 鼠模型,高迁移率族蛋白 b1 (HMGB1)-晚期糖基化终产物受体 (RAGE) 信号在 ILC2 增殖调控中的作用, 确定生存和功能。并评估 ILC2 在诱导 2 型免疫功能紊乱中的作用。 结果: HS 患者循环中 ILC2s 数量显著增加,与患者 2 型免疫反应标志物增加相关。动物研究表明,HMGB1 通过 RAGE 诱导 ILC2 在肺部蓄积,促进 ILC2 增殖,减少 ILC2 死亡。ILC2s 的扩张导致 2 型细胞因子的分泌和肺部嗜酸性粒细胞的浸润,这两者都有助于 HS 后的肺损伤。 结论: 这些结果表明,HMGB1-RAGE 信号在调节 ILC2 生物学功能中起关键作用,加重 HS 后 2 型肺部炎症。

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DOI:10.1042/BST20191010
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