CD55 upregulation in T cells of COVID-19 patients suppresses type-I interferon responses
Abstract Complement overactivation, has been verified in COVID-19 patients. Complement regulatory proteins, including CD55, control complement overactivation thus eliminating complement deposition and cell lysis. We investigated complement regulatory protein expression in COVID-19 for potential dere...
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Nature Portfolio
2025-05-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-08066-z |
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| author | Maria G. Detsika Maria Sakkou Vassiliki Triantafyllidou Dimitris Konstantopoulos Eirini Grigoriou Katherina Psarra Edison Jahaj Ioanna Dimopoulou Stylianos E. Orfanos Alexandra Tsirogianni George Kollias Anastasia Kotanidou |
| author_facet | Maria G. Detsika Maria Sakkou Vassiliki Triantafyllidou Dimitris Konstantopoulos Eirini Grigoriou Katherina Psarra Edison Jahaj Ioanna Dimopoulou Stylianos E. Orfanos Alexandra Tsirogianni George Kollias Anastasia Kotanidou |
| author_sort | Maria G. Detsika |
| collection | DOAJ |
| description | Abstract Complement overactivation, has been verified in COVID-19 patients. Complement regulatory proteins, including CD55, control complement overactivation thus eliminating complement deposition and cell lysis. We investigated complement regulatory protein expression in COVID-19 for potential deregulated expression patterns driving disease pathogenesis. Single-cell RNA-seq revealed increased PBMCs CD55 expression in severely and critically ill patients. This increase was also detected upon integrated subclustering analysis of monocyte, T cell and B cell populations. FACS analysis confirmed the significant upregulation of CD55 expression in CD4+ and CD8+ T cells and monocyte populations of severely and critically ill COVID-19 patients. This upregulation was associated with decreased expression of type-I IFN-stimulated genes (ISGs) in patients with severe and critical COVID-19, indicating a suppressor effect of CD55. Silencing of CD55 in T cells from COVID-19 severely ill patients in vitro and sensitization with SARS-CoV-2 peptides resulted in significantly augmented expression of ISGs and a reversal of their expression to levels similar to control or higher. The present study uncovers, to the best of our knowledge, a novel regulatory effect of CD55 on type-I IFN responses of severely ill COVID-19 patients, thus indicating its contribution to COVID-19 pathogenesis, and identifies a novel mechanistic pathway in the COVID-19 immune response. |
| format | Article |
| id | doaj-art-dbf253c6e88a416b9a0cd538a1328c33 |
| institution | DOAJ |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-dbf253c6e88a416b9a0cd538a1328c332025-08-20T02:55:23ZengNature PortfolioCommunications Biology2399-36422025-05-018111410.1038/s42003-025-08066-zCD55 upregulation in T cells of COVID-19 patients suppresses type-I interferon responsesMaria G. Detsika0Maria Sakkou1Vassiliki Triantafyllidou2Dimitris Konstantopoulos3Eirini Grigoriou4Katherina Psarra5Edison Jahaj6Ioanna Dimopoulou7Stylianos E. Orfanos8Alexandra Tsirogianni9George Kollias10Anastasia Kotanidou111st Department of Critical Care Medicine & Pulmonary Services, GP Livanos and M Simou Laboratories, Evangelismos Hospital, National and Kapodistrian University of AthensInstitute for Bioinnovation, Biomedical Sciences Research Center “Alexander Fleming”Institute for Bioinnovation, Biomedical Sciences Research Center “Alexander Fleming”Institute for Bioinnovation, Biomedical Sciences Research Center “Alexander Fleming”Department of Immunology and Histocompatibility, ‘Evangelismos’ General HospitalDepartment of Immunology and Histocompatibility, ‘Evangelismos’ General Hospital1st Department of Critical Care Medicine & Pulmonary Services, GP Livanos and M Simou Laboratories, Evangelismos Hospital, National and Kapodistrian University of Athens1st Department of Critical Care Medicine & Pulmonary Services, GP Livanos and M Simou Laboratories, Evangelismos Hospital, National and Kapodistrian University of Athens1st Department of Critical Care Medicine & Pulmonary Services, GP Livanos and M Simou Laboratories, Evangelismos Hospital, National and Kapodistrian University of AthensDepartment of Immunology and Histocompatibility, ‘Evangelismos’ General HospitalInstitute for Bioinnovation, Biomedical Sciences Research Center “Alexander Fleming”1st Department of Critical Care Medicine & Pulmonary Services, GP Livanos and M Simou Laboratories, Evangelismos Hospital, National and Kapodistrian University of AthensAbstract Complement overactivation, has been verified in COVID-19 patients. Complement regulatory proteins, including CD55, control complement overactivation thus eliminating complement deposition and cell lysis. We investigated complement regulatory protein expression in COVID-19 for potential deregulated expression patterns driving disease pathogenesis. Single-cell RNA-seq revealed increased PBMCs CD55 expression in severely and critically ill patients. This increase was also detected upon integrated subclustering analysis of monocyte, T cell and B cell populations. FACS analysis confirmed the significant upregulation of CD55 expression in CD4+ and CD8+ T cells and monocyte populations of severely and critically ill COVID-19 patients. This upregulation was associated with decreased expression of type-I IFN-stimulated genes (ISGs) in patients with severe and critical COVID-19, indicating a suppressor effect of CD55. Silencing of CD55 in T cells from COVID-19 severely ill patients in vitro and sensitization with SARS-CoV-2 peptides resulted in significantly augmented expression of ISGs and a reversal of their expression to levels similar to control or higher. The present study uncovers, to the best of our knowledge, a novel regulatory effect of CD55 on type-I IFN responses of severely ill COVID-19 patients, thus indicating its contribution to COVID-19 pathogenesis, and identifies a novel mechanistic pathway in the COVID-19 immune response.https://doi.org/10.1038/s42003-025-08066-z |
| spellingShingle | Maria G. Detsika Maria Sakkou Vassiliki Triantafyllidou Dimitris Konstantopoulos Eirini Grigoriou Katherina Psarra Edison Jahaj Ioanna Dimopoulou Stylianos E. Orfanos Alexandra Tsirogianni George Kollias Anastasia Kotanidou CD55 upregulation in T cells of COVID-19 patients suppresses type-I interferon responses Communications Biology |
| title | CD55 upregulation in T cells of COVID-19 patients suppresses type-I interferon responses |
| title_full | CD55 upregulation in T cells of COVID-19 patients suppresses type-I interferon responses |
| title_fullStr | CD55 upregulation in T cells of COVID-19 patients suppresses type-I interferon responses |
| title_full_unstemmed | CD55 upregulation in T cells of COVID-19 patients suppresses type-I interferon responses |
| title_short | CD55 upregulation in T cells of COVID-19 patients suppresses type-I interferon responses |
| title_sort | cd55 upregulation in t cells of covid 19 patients suppresses type i interferon responses |
| url | https://doi.org/10.1038/s42003-025-08066-z |
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