Transcriptomic analysis reveals shared deregulated neutrophil responses in COVID-19 and idiopathic pulmonary fibrosis
Abstract Background Coronavirus disease 2019 (COVID-19) is a respiratory disease linked with deregulated immune responses, leading to hyperinflammation, acute respiratory distress syndrome, and pulmonary fibrosis, often with fatal outcomes. Neutrophils play a central role in COVID-19 pathogenesis, w...
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BMC
2025-06-01
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| Series: | Respiratory Research |
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| Online Access: | https://doi.org/10.1186/s12931-025-03180-2 |
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| author | Georgios Divolis Evgenia Synolaki Rodoula Tringidou Argyrios Tzouvelekis Dimitrios T. Boumpas Panagiotis Skendros Ioanna-Evdokia Galani |
| author_facet | Georgios Divolis Evgenia Synolaki Rodoula Tringidou Argyrios Tzouvelekis Dimitrios T. Boumpas Panagiotis Skendros Ioanna-Evdokia Galani |
| author_sort | Georgios Divolis |
| collection | DOAJ |
| description | Abstract Background Coronavirus disease 2019 (COVID-19) is a respiratory disease linked with deregulated immune responses, leading to hyperinflammation, acute respiratory distress syndrome, and pulmonary fibrosis, often with fatal outcomes. Neutrophils play a central role in COVID-19 pathogenesis, with elevated peripheral blood neutrophil counts correlating with disease severity. Despite extensive research, the molecular processes associated with neutrophil hyperactivation in COVID-19 remain elusive. Methods To investigate the molecular signatures underlying neutrophil-driven pathology, we conducted transcriptome analysis in neutrophils isolated from the peripheral blood of COVID-19 patients versus healthy individuals. To evaluate the specificity of identified neutrophil signatures in COVID-19, we extended our transcriptomic analysis to neutrophils from patients with idiopathic pulmonary fibrosis (IPF), a non-infectious fibrotic lung disease. Additionally, immunofluorescence staining was performed on lung biopsy specimens from IPF patients to validate transcriptomic findings at the tissue level. Results Our analysis revealed significant transcriptional changes in COVID-19 neutrophils, particularly in pathways involved in immune regulation, inflammation, and antiviral responses. Additionally, pathways associated with autophagy and chromatin remodeling were upregulated, while translation-related processes were suppressed, indicating an increased predisposition for neutrophil extracellular trap (NET) release. This neutrophil transcriptional signature in COVID-19 appears to be associated with the previously reported deregulation of the Activin/Follistatin system in the periphery. Notably, a comparative transcriptomic analysis with neutrophils isolated from IPF patients revealed the induction of substantially overlapping inflammatory processes, suggesting common deregulated responses in COVID-19 and IPF. Consistently, significant NET formation, a hallmark of COVID-19-related inflammation, was observed within lung biopsies from IPF patients. Conclusion By delineating both shared and disease-specific molecular pathways, our findings validate the critical role of neutrophils in COVID-19 and IPF pathophysiology, highlighting their involvement in balancing the inflammatory response across diverse lung diseases. |
| format | Article |
| id | doaj-art-585c8ffaa7b446df9c59382ae07fee5e |
| institution | DOAJ |
| issn | 1465-993X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj-art-585c8ffaa7b446df9c59382ae07fee5e2025-08-20T03:21:02ZengBMCRespiratory Research1465-993X2025-06-0126111810.1186/s12931-025-03180-2Transcriptomic analysis reveals shared deregulated neutrophil responses in COVID-19 and idiopathic pulmonary fibrosisGeorgios Divolis0Evgenia Synolaki1Rodoula Tringidou2Argyrios Tzouvelekis3Dimitrios T. Boumpas4Panagiotis Skendros5Ioanna-Evdokia Galani6Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation Academy of Athens (BRFAA)Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation Academy of Athens (BRFAA)Department of Pathology, ‘Sotiria’ General Hospital of Chest DiseasesDivision of Respiratory Medicine, Medical School, University of PatrasCenter for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation Academy of Athens (BRFAA)Laboratory of Molecular Hematology, Department of Medicine, Democritus University of ThraceCenter for Basic Research, BRFAAAbstract Background Coronavirus disease 2019 (COVID-19) is a respiratory disease linked with deregulated immune responses, leading to hyperinflammation, acute respiratory distress syndrome, and pulmonary fibrosis, often with fatal outcomes. Neutrophils play a central role in COVID-19 pathogenesis, with elevated peripheral blood neutrophil counts correlating with disease severity. Despite extensive research, the molecular processes associated with neutrophil hyperactivation in COVID-19 remain elusive. Methods To investigate the molecular signatures underlying neutrophil-driven pathology, we conducted transcriptome analysis in neutrophils isolated from the peripheral blood of COVID-19 patients versus healthy individuals. To evaluate the specificity of identified neutrophil signatures in COVID-19, we extended our transcriptomic analysis to neutrophils from patients with idiopathic pulmonary fibrosis (IPF), a non-infectious fibrotic lung disease. Additionally, immunofluorescence staining was performed on lung biopsy specimens from IPF patients to validate transcriptomic findings at the tissue level. Results Our analysis revealed significant transcriptional changes in COVID-19 neutrophils, particularly in pathways involved in immune regulation, inflammation, and antiviral responses. Additionally, pathways associated with autophagy and chromatin remodeling were upregulated, while translation-related processes were suppressed, indicating an increased predisposition for neutrophil extracellular trap (NET) release. This neutrophil transcriptional signature in COVID-19 appears to be associated with the previously reported deregulation of the Activin/Follistatin system in the periphery. Notably, a comparative transcriptomic analysis with neutrophils isolated from IPF patients revealed the induction of substantially overlapping inflammatory processes, suggesting common deregulated responses in COVID-19 and IPF. Consistently, significant NET formation, a hallmark of COVID-19-related inflammation, was observed within lung biopsies from IPF patients. Conclusion By delineating both shared and disease-specific molecular pathways, our findings validate the critical role of neutrophils in COVID-19 and IPF pathophysiology, highlighting their involvement in balancing the inflammatory response across diverse lung diseases.https://doi.org/10.1186/s12931-025-03180-2NeutrophilsCOVID-19Viral infectionIdiopathic pulmonary fibrosisNETosisRNA Sequencing |
| spellingShingle | Georgios Divolis Evgenia Synolaki Rodoula Tringidou Argyrios Tzouvelekis Dimitrios T. Boumpas Panagiotis Skendros Ioanna-Evdokia Galani Transcriptomic analysis reveals shared deregulated neutrophil responses in COVID-19 and idiopathic pulmonary fibrosis Respiratory Research Neutrophils COVID-19 Viral infection Idiopathic pulmonary fibrosis NETosis RNA Sequencing |
| title | Transcriptomic analysis reveals shared deregulated neutrophil responses in COVID-19 and idiopathic pulmonary fibrosis |
| title_full | Transcriptomic analysis reveals shared deregulated neutrophil responses in COVID-19 and idiopathic pulmonary fibrosis |
| title_fullStr | Transcriptomic analysis reveals shared deregulated neutrophil responses in COVID-19 and idiopathic pulmonary fibrosis |
| title_full_unstemmed | Transcriptomic analysis reveals shared deregulated neutrophil responses in COVID-19 and idiopathic pulmonary fibrosis |
| title_short | Transcriptomic analysis reveals shared deregulated neutrophil responses in COVID-19 and idiopathic pulmonary fibrosis |
| title_sort | transcriptomic analysis reveals shared deregulated neutrophil responses in covid 19 and idiopathic pulmonary fibrosis |
| topic | Neutrophils COVID-19 Viral infection Idiopathic pulmonary fibrosis NETosis RNA Sequencing |
| url | https://doi.org/10.1186/s12931-025-03180-2 |
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