Frontiers in Immunology (Aug 2022)

PD-L1 maintains neutrophil extracellular traps release by inhibiting neutrophil autophagy in endotoxin-induced lung injury

  • Cheng-long Zhu,
  • Jian Xie,
  • Zhen-zhen Zhao,
  • Peng Li,
  • Qiang Liu,
  • Yu Guo,
  • Yan Meng,
  • Xiao-jian Wan,
  • Jin-jun Bian,
  • Xiao-ming Deng,
  • Jia-feng Wang

DOI
https://doi.org/10.3389/fimmu.2022.949217
Journal volume & issue
Vol. 13

Abstract

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Programmed death ligand 1 (PD-L1) is not only an important molecule in mediating tumor immune escape, but also regulates inflammation development. Here we showed that PD-L1 was upregulated on neutrophils in lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS). Neutrophil specific knockout of PD-L1 reduced lung injury in ARDS model induced by intratracheal LPS injection. The level of NET release was reduced and autophagy is elevated by PD-L1 knockout in ARDS neutrophils both in vivo and in vitro. Inhibition of autophagy could reverse the inhibitory effect of PD-L1 knockout on NET release. PD-L1 interacted with p85 subunit of PI3K at the endoplasmic reticulum (ER) in neutrophils from ARDS patients, activating the PI3K/Akt/mTOR pathway. An extrinsic neutralizing antibody against PD-L1 showed a protective effect against ARDS. Together, PD-L1 maintains the release of NETs by regulating autophagy through the PI3K/Akt/mTOR pathway in ARDS. Anti-PD-L1 therapy may be a promising measure in treating ARDS.

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