ArticleAmerican journal of physiology. Lung cellular and molecular physiology2020
Blockade of endothelial, but not epithelial, cell expression of PD-L1 following severe shock attenuates the development of indirect acute lung injury in mice.
Article in American journal of physiology. Lung cellular and molecular physiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- Endothelial cell, but not neutrophil, programmed cell death receptor-ligand 1 loss has a morbid impact on experimental murine shock/sepsis-induced lung injury.Frontiers in immunology · 2026Article
- Differential Effects of Endothelial Cell- as opposed to Neutrophil-Lineage Restricted PD-L1 Gene Expression on Experimental Murine Shock/ Sepsis-Induced Lung Injury.Research square · 2025Article
- Mechanisms of immune suppression in sepsis/shock: one investigator's/lab group's experience (SLB 2024 legacy award presentation).Journal of leukocyte biology · 2025Article
- VISTA nonredundantly regulates proliferation and CD69low γδ T cell accumulation in the intestine in murine sepsis.Journal of leukocyte biology · 2024Article
- Tiny Guides, Big Impact: Focus on the Opportunities and Challenges of miR-Based Treatments for ARDS.International journal of molecular sciences · 2024Review
- Article
- PKM2/STAT1-mediated PD-L1 upregulation on neutrophils during sepsis promotes neutrophil organ accumulation by serving an anti-apoptotic role.Journal of inflammation (London, England) · 2023Article
- Progress in non-viral localized delivery of siRNA therapeutics for pulmonary diseases.Acta pharmaceutica Sinica. B · 2023Review
- Forsythiaside A prevents zymosan A-induced cell migration in neutrophil-differentiated HL-60 cells via PD-1/PD-L1 pathway.Heliyon · 2023Article
- siRNA-MediatedInternational journal of molecular sciences · 2023Article
- The implication of targeting PD-1:PD-L1 pathway in treating sepsis through immunostimulatory and anti-inflammatory pathways.Frontiers in immunology · 2023Review
- Role of regulation of PD-1 and PD-L1 expression in sepsis.Frontiers in immunology · 2023Review
- Tight Junctions, the Epithelial Barrier, and Toll-like Receptor-4 During Lung Injury.Inflammation · 2022Review
- The miR-199a-5p/PD-L1 axis regulates cell proliferation, migration and invasion in follicular thyroid carcinoma.BMC cancer · 2022Article
- Pulmonary delivery of siRNA against acute lung injury/acute respiratory distress syndrome.Acta pharmaceutica Sinica. B · 2022Review
- Dexmedetomidine Attenuates LPS-Stimulated Alveolar Type II Cells' Injury through Upregulation of miR-140-3p and Partial Suppression of PD-L1 Involving Inactivating JNK-Bnip3 Pathway.Canadian respiratory journal · 2022Article
- Negative Immune Checkpoint Protein, VISTA, Regulates the CD4Frontiers in immunology · 2022Article
- The pathogenic role of epithelial and endothelial cells in early-phase COVID-19 pneumonia: victims and partners in crime.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2021Review
- Concentrated Secretome of Adipose Stromal Cells Limits Influenza A Virus-Induced Lung Injury in Mice.Cells · 2021Article
- Covid-19 Interstitial Pneumonia: Histological and Immunohistochemical Features on Cryobiopsies.Respiration; international review of thoracic diseases · 2021Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
This study sets out to establish the comparative contribution of PD-L1 expression by pulmonary endothelial cells (ECs) and/or epithelial cells (EpiCs) to the development of indirect acute lung injury (iALI) by taking advantage of the observation that treatment with naked siRNA by intratracheal delivery in mice primarily affects lung EpiCs, but not lung ECs, while intravenous delivery of liposomal-encapsulated siRNA largely targets vascular ECs including the lung, but not pulmonary EpiCs. We showed that using a mouse model of iALI [induced by hemorrhagic shock followed by septic challenge (Hem-CLP)], PD-L1 expression on pulmonary ECs or EpiCs was significantly upregulated in the iALI mice at 24 h post-septic insult. After documenting the selective ability of intratracheal versus intravenous delivery of PD-L1 siRNA to inhibit PD-L1 expression on EpiCs versus ECs, respectively, we observed that the iALI-induced elevation of cytokine/chemokine levels (in the bronchoalveolar lavage fluid, lung lysates, or plasma), lung myeloperoxidase and caspase-3 activities could largely only be inhibited by intravenous, but not intratracheal, delivery of PD-L1 siRNA. Moreover, intravenous, but not intratracheal, delivery led to a preservation of normal tissue architecture, lessened pulmonary edema, and reduced neutrophils influx induced by iALI. In addition, in vitro mouse endothelial cell line studies showed that PD-L1 gene knockdown by siRNA or knockout by CRISPR/Cas9-mediated gene manipulation, reduced monolayer permeability, and maintained tight junction protein levels upon recombinant IFN-γ stimulation. Together, these data imply a critical role for pulmonary vascular ECs in mediating PD-1:PD-L1-driven pathological changes resulting from systemic stimuli such as Hem-CLP.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.