Immunological Similarities and Differences between Post-COVID-19 Lung Sequelae and Idiopathic Pulmonary Fibrosis
Introduction: Pulmonary fibrosis is an irreversible condition that may be caused by known (including viral triggers such as SARS-CoV-2) and unknown insults. The latter group includes idiopathic pulmonary fibrosis (IPF), which is a chronic, progressive fibrosing interstitial pneumonia of unknown caus...
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MDPI AG
2024-03-01
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| Online Access: | https://www.mdpi.com/2227-9059/12/3/630 |
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| author | Sara Gangi Laura Bergantini Paolo Cameli Irene Paggi Marco Spalletti Fabrizio Mezzasalma Elena Bargagli Miriana d’Alessandro |
| author_facet | Sara Gangi Laura Bergantini Paolo Cameli Irene Paggi Marco Spalletti Fabrizio Mezzasalma Elena Bargagli Miriana d’Alessandro |
| author_sort | Sara Gangi |
| collection | DOAJ |
| description | Introduction: Pulmonary fibrosis is an irreversible condition that may be caused by known (including viral triggers such as SARS-CoV-2) and unknown insults. The latter group includes idiopathic pulmonary fibrosis (IPF), which is a chronic, progressive fibrosing interstitial pneumonia of unknown cause. The longer the insult acts on lung tissue, the lower the probability of a complete resolution of the damage. An emerging clinical entity post-COVID-19 is pulmonary fibrosis (PCPF), which shares many pathological, clinical, and immunological features with IPF. The fibrotic response in both diseases—IPF and PCPF—is orchestrated in part by the immune system. An important role regarding the inhibitory or stimulatory effects on immune responses is exerted by the immune checkpoints (ICs). The aim of the present study was to analyse the similarities and differences between CD4+, CD8+, and NK cells in the peripheral blood of patients affected by fibrotic disease, IPF, and PCPF compared with sarcoidosis patients and healthy controls. The second aim was to evaluate the expression and co-expression of PD-1 and TIGIT on CD4, CD8, and NK cells from our patient cohort. Methods: One hundred and fifteen patients affected by IPF, PCPF, and sarcoidosis at the rare pulmonary disease centre of the University of Siena were enrolled. Forty-eight patients had an IPF diagnosis, 55 had PCPF, and 12 had sarcoidosis. Further, ten healthy controls were enrolled. PCPF patients were included between 6 and 9 months following hospital discharge for COVID-19. The peripheral blood samples were collected, and through flow cytometric analysis, we analysed the expression of CD4, CD8, NK cells, PD-1, and TIGIT. Results: The results show a greater depletion of CD4 and NK cells in IPF patients compared to other groups (<i>p</i> = 0.003), in contrast with CD8 cells (<i>p</i> < 001). Correlation analysis demonstrated an indirect correlation between CD4 and CD8 cells in IPF and sarcoidosis patients (<i>p</i> < 0.001 = −0.87 and <i>p</i> = 0.042; r = −0.6, respectively). Conversely, PCPF patients revealed a direct correlation between CD4 and CD8 cells (<i>p</i> < 0.001; r = 0.90) accentuating an immune response restoration. The expression of PD-1 and TIGIT was abundant on T and NK cell subsets of the two lung fibrotic groups, IPF and PCPF. Analogously, the co-expression of PD-1 and TIGIT on the surfaces of CD4 and CD8 were increased in such diseases. <b>Conclusions</b>: Our study shines a spotlight on the immune responses involved in the development of pulmonary fibrosis, idiopathic and secondary to SARS-CoV-2 infection. We observed a significant imbalance not only in CD4, CD8, and NK blood percentages in IPF and PCPF patients but also in their functional phenotypes evaluated through the expression of ICs. |
| first_indexed | 2024-04-24T18:31:26Z |
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| series | Biomedicines |
| spelling | doaj.art-9c6a3633c2d44b189343dd0935c869652024-03-27T13:22:59ZengMDPI AGBiomedicines2227-90592024-03-0112363010.3390/biomedicines12030630Immunological Similarities and Differences between Post-COVID-19 Lung Sequelae and Idiopathic Pulmonary FibrosisSara Gangi0Laura Bergantini1Paolo Cameli2Irene Paggi3Marco Spalletti4Fabrizio Mezzasalma5Elena Bargagli6Miriana d’Alessandro7Respiratory Diseases and Lung Transplantation Unit, Department of Medical and Surgical Sciences & Neuro-Sciences, University of Siena, 53100 Siena, ItalyRespiratory Diseases and Lung Transplantation Unit, Department of Medical and Surgical Sciences & Neuro-Sciences, University of Siena, 53100 Siena, ItalyRespiratory Diseases and Lung Transplantation Unit, Department of Medical and Surgical Sciences & Neuro-Sciences, University of Siena, 53100 Siena, ItalyRespiratory Diseases and Lung Transplantation Unit, Department of Medical and Surgical Sciences & Neuro-Sciences, University of Siena, 53100 Siena, ItalyRespiratory Diseases and Lung Transplantation Unit, Department of Medical and Surgical Sciences & Neuro-Sciences, University of Siena, 53100 Siena, ItalyDiagnostic and Interventional Bronchoscopy Unit, Cardio-Thoracic and Vascular Department, University Hospital of Siena, Azienda Ospedaliera Universitaria Senese—AOUS, 53100 Siena, ItalyRespiratory Diseases and Lung Transplantation Unit, Department of Medical and Surgical Sciences & Neuro-Sciences, University of Siena, 53100 Siena, ItalyRespiratory Diseases and Lung Transplantation Unit, Department of Medical and Surgical Sciences & Neuro-Sciences, University of Siena, 53100 Siena, ItalyIntroduction: Pulmonary fibrosis is an irreversible condition that may be caused by known (including viral triggers such as SARS-CoV-2) and unknown insults. The latter group includes idiopathic pulmonary fibrosis (IPF), which is a chronic, progressive fibrosing interstitial pneumonia of unknown cause. The longer the insult acts on lung tissue, the lower the probability of a complete resolution of the damage. An emerging clinical entity post-COVID-19 is pulmonary fibrosis (PCPF), which shares many pathological, clinical, and immunological features with IPF. The fibrotic response in both diseases—IPF and PCPF—is orchestrated in part by the immune system. An important role regarding the inhibitory or stimulatory effects on immune responses is exerted by the immune checkpoints (ICs). The aim of the present study was to analyse the similarities and differences between CD4+, CD8+, and NK cells in the peripheral blood of patients affected by fibrotic disease, IPF, and PCPF compared with sarcoidosis patients and healthy controls. The second aim was to evaluate the expression and co-expression of PD-1 and TIGIT on CD4, CD8, and NK cells from our patient cohort. Methods: One hundred and fifteen patients affected by IPF, PCPF, and sarcoidosis at the rare pulmonary disease centre of the University of Siena were enrolled. Forty-eight patients had an IPF diagnosis, 55 had PCPF, and 12 had sarcoidosis. Further, ten healthy controls were enrolled. PCPF patients were included between 6 and 9 months following hospital discharge for COVID-19. The peripheral blood samples were collected, and through flow cytometric analysis, we analysed the expression of CD4, CD8, NK cells, PD-1, and TIGIT. Results: The results show a greater depletion of CD4 and NK cells in IPF patients compared to other groups (<i>p</i> = 0.003), in contrast with CD8 cells (<i>p</i> < 001). Correlation analysis demonstrated an indirect correlation between CD4 and CD8 cells in IPF and sarcoidosis patients (<i>p</i> < 0.001 = −0.87 and <i>p</i> = 0.042; r = −0.6, respectively). Conversely, PCPF patients revealed a direct correlation between CD4 and CD8 cells (<i>p</i> < 0.001; r = 0.90) accentuating an immune response restoration. The expression of PD-1 and TIGIT was abundant on T and NK cell subsets of the two lung fibrotic groups, IPF and PCPF. Analogously, the co-expression of PD-1 and TIGIT on the surfaces of CD4 and CD8 were increased in such diseases. <b>Conclusions</b>: Our study shines a spotlight on the immune responses involved in the development of pulmonary fibrosis, idiopathic and secondary to SARS-CoV-2 infection. We observed a significant imbalance not only in CD4, CD8, and NK blood percentages in IPF and PCPF patients but also in their functional phenotypes evaluated through the expression of ICs.https://www.mdpi.com/2227-9059/12/3/630idiopathic pulmonary fibrosispost-COVID pulmonary fibrosisimmune cellsimmune checkpointCD4CD8 |
| spellingShingle | Sara Gangi Laura Bergantini Paolo Cameli Irene Paggi Marco Spalletti Fabrizio Mezzasalma Elena Bargagli Miriana d’Alessandro Immunological Similarities and Differences between Post-COVID-19 Lung Sequelae and Idiopathic Pulmonary Fibrosis Biomedicines idiopathic pulmonary fibrosis post-COVID pulmonary fibrosis immune cells immune checkpoint CD4 CD8 |
| title | Immunological Similarities and Differences between Post-COVID-19 Lung Sequelae and Idiopathic Pulmonary Fibrosis |
| title_full | Immunological Similarities and Differences between Post-COVID-19 Lung Sequelae and Idiopathic Pulmonary Fibrosis |
| title_fullStr | Immunological Similarities and Differences between Post-COVID-19 Lung Sequelae and Idiopathic Pulmonary Fibrosis |
| title_full_unstemmed | Immunological Similarities and Differences between Post-COVID-19 Lung Sequelae and Idiopathic Pulmonary Fibrosis |
| title_short | Immunological Similarities and Differences between Post-COVID-19 Lung Sequelae and Idiopathic Pulmonary Fibrosis |
| title_sort | immunological similarities and differences between post covid 19 lung sequelae and idiopathic pulmonary fibrosis |
| topic | idiopathic pulmonary fibrosis post-COVID pulmonary fibrosis immune cells immune checkpoint CD4 CD8 |
| url | https://www.mdpi.com/2227-9059/12/3/630 |
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