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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.949217/full |
| _version_ | 1811242671415492608 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Cheng-long Zhu |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T13:54:31Z |
| format | Article |
| id | doaj.art-f092dafe2a51403b8dd5f71dba41bbf7 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T13:54:31Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-f092dafe2a51403b8dd5f71dba41bbf72022-12-22T03:30:25ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-08-011310.3389/fimmu.2022.949217949217PD-L1 maintains neutrophil extracellular traps release by inhibiting neutrophil autophagy in endotoxin-induced lung injuryCheng-long ZhuJian XieZhen-zhen ZhaoPeng LiQiang LiuYu GuoYan MengXiao-jian WanJin-jun BianXiao-ming DengJia-feng WangProgrammed 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.https://www.frontiersin.org/articles/10.3389/fimmu.2022.949217/fullARDSPD-L1autophagyneutrophilsneutrophil extracellular trapsanti-PD-L1 therapy |
| spellingShingle | 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 PD-L1 maintains neutrophil extracellular traps release by inhibiting neutrophil autophagy in endotoxin-induced lung injury Frontiers in Immunology ARDS PD-L1 autophagy neutrophils neutrophil extracellular traps anti-PD-L1 therapy |
| 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 | ARDS PD-L1 autophagy neutrophils neutrophil extracellular traps anti-PD-L1 therapy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.949217/full |
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