ArticleThe European respiratory journal2022
Macrophage-derived IL-6 trans-signalling as a novel target in the pathogenesis of bronchopulmonary dysplasia.
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Article in The European respiratory journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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80 citing papers in PubMed, 113 citations in OpenAlex.
- Respiratory mucosal immunity: Biological functions, diseases, prevention and therapy.Genes & diseases · 2026Review
- Refining therapeutic targeting of interleukin-6 by signalling mode selectivity.Nature reviews. Drug discovery · 2026Review
- Novel netrin-1-Unc5b-Klf4 axis balances AT2 survival in experimental bronchopulmonary dysplasia.American journal of respiratory cell and molecular biology · 2026Article
- Mesenchyme-derived inflammation during the saccular stage recruits macrophages and alters lung development.JCI insight · 2026Article
- The autonomic nervous system-lung interface in experimental BPD: NPY modulates immune response, alveolar growth and vascular muscularizationin neonatal mice exposed to oxidative stress.Respiratory research · 2026Article
- Impact of resuscitation with 100% oxygen during physiological-based cord clamping or immediate cord clamping on lung inflammation and injury.Pediatric research · 2026Article
- Prenatal non-infectious mild stressor modulates early-life lung development in a time-specific manner.Respiratory research · 2026Article
- Ginkgolide B Alleviates Airway Inflammation in Hyperoxia Lung Injury.Immunity, inflammation and disease · 2026Article
- Near-Infrared Laser Photobiomodulation Reduces Pro-Inflammatory Cytokines in an In Vitro Model of Bronchopulmonary Dysplasia: A Preliminary Report.Medical sciences (Basel, Switzerland) · 2026Article
- PKM2 Promotes Glycolysis in Alveolar Macrophages and Induces Inflammation in Bronchopulmonary Dysplasia.Inflammation · 2026Article
- The evolving pathophysiology of bronchopulmonary dysplasia.Physiological reviews · 2026Review
- Dermal Fibroblasts-derived Exosomes Alleviated Bronchopulmonary Dysplasia in Neonatal Rats Partially by Regulating Autophagy.Current stem cell research & therapy · 2026Article
- Downregulation of UNC5B-AS1 in Preterm Infants with Bronchopulmonary Dysplasia and Its Protective Mechanism via the miR-134-5p/IGF1 Axis.Journal of inflammation research · 2026Article
- Role of connexin 43 in hyperoxia-induced bronchopulmonary dysplasia and associated pulmonary hypertension.PloS one · 2026Article
- Interleukin-6 in complications of prematurity: from biomarker to targeted therapy.Frontiers in pediatrics · 2026Review
- Mitochondrial quality control mechanisms as molecular targets for impaired lung development: from fetuses to neonates.Respiratory research · 2025Review
- Prenatal lipopolysaccharide exposure programs the early-life lung development by modulating mesenchymal fibroblasts in a time- and dose-dependent manner.BMC medicine · 2025Article
- GSDMD deficiency attenuates BPD by suppressing macrophage pyroptosis and promoting M2 polarization.Cell death discovery · 2025Article
- Targeting IL6-Edn1-FoxO1 axis enables lung growth in mechanically ventilated newborn mice.The European respiratory journal · 2025Article
- Farber's Lipogranulomatosis: Multimodal Therapy With Tocilizumab and Consolidative HSCT Improves Assessment, and Long-Term Outcome.JIMD reports · 2025Article
20 more citing papers are in PubMed but not listed here.
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Authors and funding
23 authors at 6 institutions in 2 countries.
Dharmesh HiraniUniversity of Cologne, Faculty of Medicine and University Hospital Cologne, Translational Experimental Pediatrics - Experimental Pulmonology, Dept of Pediatric and Adolescent Medicine, Cologne, Germany.
Cristina M AlviraDept of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
Soula DanopoulosLundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
Carlos MillaDept of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
Michele DonatoBiomedical Informatics Research-Institute for Immunity, Transplantation, and Infection, Stanford University, Stanford, CA, USA.
Lu TianDept of Biomedical Data Science, Stanford University, Stanford, CA, USA.
Jasmine MohrUniversity of Cologne, Faculty of Medicine and University Hospital Cologne, Translational Experimental Pediatrics - Experimental Pulmonology, Dept of Pediatric and Adolescent Medicine, Cologne, Germany.
Katharina DingerUniversity of Cologne, Faculty of Medicine and University Hospital Cologne, Translational Experimental Pediatrics - Experimental Pulmonology, Dept of Pediatric and Adolescent Medicine, Cologne, Germany.
Christina VohlenUniversity of Cologne, Faculty of Medicine and University Hospital Cologne, Translational Experimental Pediatrics - Experimental Pulmonology, Dept of Pediatric and Adolescent Medicine, Cologne, Germany.
Jaco SelleUniversity of Cologne, Faculty of Medicine and University Hospital Cologne, Translational Experimental Pediatrics - Experimental Pulmonology, Dept of Pediatric and Adolescent Medicine, Cologne, Germany.
Silke V Koningsbruggen-RietschelUniversity of Cologne, Faculty of Medicine and University Hospital Cologne, Dept of Pediatric and Adolescent Medicine, Cologne, Germany.
Verena BarbarinoDept I of Internal Medicine, Center for Integrated Oncology (CIO) Köln-Bonn, University of Cologne, Cologne, Germany.
Christian PallaschDept I of Internal Medicine, Center for Integrated Oncology (CIO) Köln-Bonn, University of Cologne, Cologne, Germany.
Stefan Rose-JohnInstitute of Biochemistry, Christian-Albrechts-University Kiel, Kiel, Germany.
Margarete OdenthalUniversity of Cologne, Faculty of Medicine and University Hospital Cologne, Institute for Pathology, Cologne, Germany.
Gloria S PryhuberDivision of Neonatology, Dep of Pediatrics, University of Rochester Medical Center, Rochester, NY, USA.ORCID 0000-0002-9185-3994
Siavash MansouriDept of Lung Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Member of the German Center for Lung Research (DZL), Bad Nauheim, Germany.
Rajkumar SavaiDept of Lung Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Member of the German Center for Lung Research (DZL), Bad Nauheim, Germany.ORCID 0000-0003-1538-2091
Werner SeegerDept of Lung Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Member of the German Center for Lung Research (DZL), Bad Nauheim, Germany.ORCID 0000-0003-1946-0894
Purvesh KhatriBiomedical Informatics Research-Institute for Immunity, Transplantation, and Infection, Stanford University, Stanford, CA, USA.
Denise Al AlamLundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.ORCID 0000-0003-3148-7352
Jörg DötschUniversity of Cologne, Faculty of Medicine and University Hospital Cologne, Dept of Pediatric and Adolescent Medicine, Cologne, Germany.
Miguel A Alejandre AlcazarUniversity of Cologne, Faculty of Medicine and University Hospital Cologne, Translational Experimental Pediatrics - Experimental Pulmonology, Dept of Pediatric and Adolescent Medicine, Cologne, Germany miguel.alejandre-alcazar@uk-koeln.de.
University of Cologne · DEStanford University · USMax Planck Institute for Heart and Lung Research · DEUCLA Medical Center · USChristian-Albrechts-Universität zu Kiel · DEUniversity of Rochester Medical Center · US
Funding
BioRepository for INvestigation of Diseases of the Lung (BRINDL) - Phase IIIU01HL148861 · NHLBI · UNIVERSITY OF ROCHESTER · PI GLORIA S PRYHUBER · 2019 to 2026
$9.7MMolecular Atlas of Lung Development - Data Coordinating CenterU01HL122638 · NHLBI · DUKE UNIVERSITY · PI CLARK, ROBERT F, PALMER, SCOTT M · 2014 to 2018
$7.5MBiorepository for Investigation of Neonatal Diseases of Lung-Normal (BRINDL-NL)U01HL122700 · NHLBI · UNIVERSITY OF ROCHESTER · PI PRYHUBER, GLORIA S · 2014 to 2018
$6.1MMolecular anatomy of human alveolar developmentU01HL122681 · NHLBI · CHILDREN'S HOSPITAL OF LOS ANGELES · PI WARBURTON, DAVID · 2014 to 2018
$4.0MType I IFN signaling during lung development in Down Syndrome-Multiome sequencing of human fetal and pediatric trisomy 21 lungsR01HL155104 · NHLBI · LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER · PI DANOPOULOS, SOULA ATHANASIA · 2021 to 2025
$3.3MMechanisms controlling early human lung developmentR01HL141856 · NHLBI · LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER · PI AL-ALAM, DENISE · 2018 to 2022
$2.5MNovel Molecular Mechanisms Regulating Postnatal Pulmonary AngiogenesisR01HL122918 · NHLBI · STANFORD UNIVERSITY · PI ALVIRA, CRISTINA MARIA · 2014 to 2018
$2.3MNHLBI NIH HHS R01 HL122918NHLBI NIH HHS R01 HL141856NHLBI NIH HHS R01 HL155104NHLBI NIH HHS U01 HL122638NHLBI NIH HHS U01 HL122681NHLBI NIH HHS U01 HL122700NHLBI NIH HHS U01 HL148861
Abstract
rationalePremature infants exposed to oxygen are at risk for bronchopulmonary dysplasia (BPD), which is characterised by lung growth arrest. Inflammation is important, but the mechanisms remain elusive. Here, we investigated inflammatory pathways and therapeutic targets in severe clinical and experimental BPD. METHODS AND
resultsFirst, transcriptomic analysis with
conclusionWe present a novel IL-6-mediated mechanism by which hyperoxia activates macrophages in immature lungs, impairs ATII homeostasis and disrupts elastic fibre formation, thereby inhibiting lung growth. The data provide evidence that IL-6 trans-signalling could offer an innovative pharmacological target to enable lung growth in severe neonatal chronic lung disease.
Indexed as
Bronchopulmonary DysplasiaHyperoxiaAnimalsAnimals, NewbornDisease Models, AnimalInterleukin-6LungMacrophagesMiceInterleukin-6
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