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

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 speci...

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Autores principales: Zhu, Cheng-long, Xie, Jian, Zhao, Zhen-zhen, Li, Peng, Liu, Qiang, Guo, Yu, Meng, Yan, Wan, Xiao-jian, Bian, Jin-jun, Deng, Xiao-ming, Wang, Jia-feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9396256/
https://www.ncbi.nlm.nih.gov/pubmed/36016930
http://dx.doi.org/10.3389/fimmu.2022.949217
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author Zhu, Cheng-long
Xie, Jian
Zhao, Zhen-zhen
Li, Peng
Liu, Qiang
Guo, Yu
Meng, Yan
Wan, Xiao-jian
Bian, Jin-jun
Deng, Xiao-ming
Wang, Jia-feng
author_facet Zhu, Cheng-long
Xie, Jian
Zhao, Zhen-zhen
Li, Peng
Liu, Qiang
Guo, Yu
Meng, Yan
Wan, Xiao-jian
Bian, Jin-jun
Deng, Xiao-ming
Wang, Jia-feng
author_sort Zhu, Cheng-long
collection PubMed
description 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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spelling pubmed-93962562022-08-24 PD-L1 maintains neutrophil extracellular traps release by inhibiting neutrophil autophagy in endotoxin-induced lung injury Zhu, Cheng-long Xie, Jian Zhao, Zhen-zhen Li, Peng Liu, Qiang Guo, Yu Meng, Yan Wan, Xiao-jian Bian, Jin-jun Deng, Xiao-ming Wang, Jia-feng Front Immunol Immunology 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. Frontiers Media S.A. 2022-08-09 /pmc/articles/PMC9396256/ /pubmed/36016930 http://dx.doi.org/10.3389/fimmu.2022.949217 Text en Copyright © 2022 Zhu, Xie, Zhao, Li, Liu, Guo, Meng, Wan, Bian, Deng and Wang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Zhu, Cheng-long
Xie, Jian
Zhao, Zhen-zhen
Li, Peng
Liu, Qiang
Guo, Yu
Meng, Yan
Wan, Xiao-jian
Bian, Jin-jun
Deng, Xiao-ming
Wang, Jia-feng
PD-L1 maintains neutrophil extracellular traps release by inhibiting neutrophil autophagy in endotoxin-induced lung injury
title PD-L1 maintains neutrophil extracellular traps release by inhibiting neutrophil autophagy in endotoxin-induced lung injury
title_full PD-L1 maintains neutrophil extracellular traps release by inhibiting neutrophil autophagy in endotoxin-induced lung injury
title_fullStr PD-L1 maintains neutrophil extracellular traps release by inhibiting neutrophil autophagy in endotoxin-induced lung injury
title_full_unstemmed PD-L1 maintains neutrophil extracellular traps release by inhibiting neutrophil autophagy in endotoxin-induced lung injury
title_short PD-L1 maintains neutrophil extracellular traps release by inhibiting neutrophil autophagy in endotoxin-induced lung injury
title_sort pd-l1 maintains neutrophil extracellular traps release by inhibiting neutrophil autophagy in endotoxin-induced lung injury
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9396256/
https://www.ncbi.nlm.nih.gov/pubmed/36016930
http://dx.doi.org/10.3389/fimmu.2022.949217
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