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|Title:||Blockade of PD-1 decreases neutrophilic inflammation and lung damage in experimental COPD|
Menger, Michael D.
Bohle, Rainer M.
|Title:||American Journal of Physiology. Lung Cellular and Molecular Physiology|
|Publisher/Platform:||American Physiological Society|
|Year of Publication:||2021|
|Free key words:||COPD|
|DDC notations:||610 Medicine and health|
|Publikation type:||Journal Article|
|Abstract:||Chronic obstructive lung disease (COPD) and lung cancer are both caused by smoking and often occur as comorbidity. The programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) axis is an important canonic immunoregulatory pathway, and antibodies that specifically block PD-1 or PD-L1 have demonstrated efficacy as therapeutic agents for non-small cell lung cancer. The role of the PD-1/PD-L1 axis in the pathogenesis of COPD is unknown. Here, we analyzed the function of the PD-1/PD-L1 axis in preclinical COPD models and evaluated the concentrations of PD-1 and PD-L1 in human serum and bronchoalveolar lavage (BAL) fluids as biomarkers for COPD. Anti-PD-1 treatment decreased lung damage and neutrophilic inflammation in mice chronically exposed to cigarette smoke (CS) or nontypeable Haemophilus influenzae (NTHi). Ex vivo stimulated macrophages obtained from anti-PD-1-treated mice released reduced amounts of inflammatory cytokines. PD-L1 concentrations correlated positively with PD-1 concentrations in human serum and BAL fluids. Lung sections obtained from patients with COPD stained positive for PD-L1. Our data indicate that the PD-1/PD-L1 axis is involved in developing inflammation and tissue destruction in COPD. Inflammation-induced activation of the PD-1 pathway may contribute to disease progression.|
|DOI of the first publication:||10.1152/ajplung.00121.2020|
|URL of the first publication:||https://journals.physiology.org/doi/full/10.1152/ajplung.00121.2020|
|Link to this record:||urn:nbn:de:bsz:291--ds-367634|
|Date of registration:||11-Jul-2022|
|Description of the related object:||Supplemental material|
|Faculty:||M - Medizinische Fakultät|
|Department:||M - Biophysik|
M - Chirurgie
M - Innere Medizin
M - Pathologie
|Professorship:||M - Prof. Dr. Robert Bals|
M - Prof. Dr. Rainer M. Bohle
M - Prof. Dr. Markus Hoth
M - Prof. Dr. Michael D. Menger
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