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.

中文翻译：

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RAGE诱导的ILC2在失血性休克引起的急性肺损伤中扩增


背景 2 型免疫功能障碍会导致失血性休克 (HS) 和创伤后的急性肺损伤和死亡。第 2 类先天淋巴细胞 (ILC2) 在调节 2 型免疫反应中发挥着重要作用。然而，ILC2在HS后急性肺损伤中的作用及其潜在机制尚未阐明。目的 探讨ILC2在热射病急性肺损伤中的调节作用及其在患者和动物模型中的作用机制。方法 对 HS 患者和健康对照的 2 型免疫反应循环标志物进行了表征。使用 HS 小鼠模型，确定了晚期糖基化终末产物 (RAGE) 信号传导的高迁移率族盒 1 (HMGB1) 受体在调节 ILC2 增殖、存活和功能中的作用。还评估了 ILC2 在诱导 2 型免疫功能障碍中的作用。结果 HS患者循环中ILC2的数量显着增加，这与患者2型免疫反应标志物的增加相关。动物研究表明，HMGB1 通过 RAGE 发挥作用，通过促进 ILC2 增殖和减少 ILC2 死亡来诱导 ILC2 在肺部积聚。 ILC2 的扩增导致 2 型细胞因子分泌和肺部嗜酸性粒细胞浸润，这两者均导致 HS 后的肺损伤。结论 这些结果表明 HMGB1-RAGE 信号在调节 ILC2 生物学功能中发挥关键作用，从而加重 HS 后的 2 型肺部炎症。