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

Kai Zhang, Yue Jin, Dengming Lai, Jieyan Wang, Yang Wang, Xiaoliang Wu, Melanie Scott, Yuehua Li, Jinchao Hou, Timothy Billiar, Mark Wilson, Qiang Shu, Xiangming Fang, Jie Fan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

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.

Original languageEnglish
Pages (from-to)209-219
Number of pages11
JournalThorax
Volume75
Issue number3
DOIs
StatePublished - 1 Mar 2020
Externally publishedYes

Keywords

  • ARDS
  • critical care
  • cytokine biology
  • innate immunity

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