Bronchoalveolar Tregs are associated with duration of mechanical ventilation in acute respiratory distress syndrome
Abstract Background Foxp3+ regulatory T cells (Tregs) play essential roles in immune homeostasis and repair of damaged lung tissue. We hypothesized that patients whose lung injury resolves quickly, as measured by time to liberation from mechanical ventilation, have a higher percentage of Tregs among...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-11-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12967-020-02595-3 |
| _version_ | 1818187860120961024 |
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| author | Dustin L. Norton Agathe Ceppe Miriya K. Tune Matthew McCravy Thomas Devlin M. Bradley Drummond Shannon S. Carson Benjamin G. Vincent Robert S. Hagan Hong Dang Claire M. Doerschuk Jason R. Mock |
| author_facet | Dustin L. Norton Agathe Ceppe Miriya K. Tune Matthew McCravy Thomas Devlin M. Bradley Drummond Shannon S. Carson Benjamin G. Vincent Robert S. Hagan Hong Dang Claire M. Doerschuk Jason R. Mock |
| author_sort | Dustin L. Norton |
| collection | DOAJ |
| description | Abstract Background Foxp3+ regulatory T cells (Tregs) play essential roles in immune homeostasis and repair of damaged lung tissue. We hypothesized that patients whose lung injury resolves quickly, as measured by time to liberation from mechanical ventilation, have a higher percentage of Tregs amongst CD4+ T cells in either airway, bronchoalveolar lavage (BAL) or peripheral blood samples. Methods We prospectively enrolled patients with ARDS requiring mechanical ventilation and collected serial samples, the first within 72 h of ARDS diagnosis (day 0) and the second 48–96 h later (day 3). We analyzed immune cell populations and cytokines in BAL, tracheal aspirates and peripheral blood, as well as cytokines in plasma, obtained at the time of bronchoscopy. The study cohort was divided into fast resolvers (FR; n = 8) and slow resolvers (SR; n = 5), based on the median number of days until first extubation for all participants (n = 13). The primary measure was the percentage of CD4+ T cells that were Tregs. Results The BAL of FR contained more Tregs than SR. This finding did not extend to Tregs in tracheal aspirates or blood. BAL Tregs expressed more of the full-length FOXP3 than a splice variant missing exon 2 compared to Tregs in simultaneously obtained peripheral blood. Conclusion Tregs are present in the bronchoalveolar space during ARDS. A greater percentage of CD4+ cells were Tregs in the BAL of FR than SR. Tregs may play a role in the resolution of ARDS, and enhancing their numbers or functions may be a therapeutic target. |
| first_indexed | 2024-12-11T23:17:44Z |
| format | Article |
| id | doaj.art-450aa140b416454e9d633853381d0299 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-11T23:17:44Z |
| publishDate | 2020-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-450aa140b416454e9d633853381d02992022-12-22T00:46:27ZengBMCJournal of Translational Medicine1479-58762020-11-0118111710.1186/s12967-020-02595-3Bronchoalveolar Tregs are associated with duration of mechanical ventilation in acute respiratory distress syndromeDustin L. Norton0Agathe Ceppe1Miriya K. Tune2Matthew McCravy3Thomas Devlin4M. Bradley Drummond5Shannon S. Carson6Benjamin G. Vincent7Robert S. Hagan8Hong Dang9Claire M. Doerschuk10Jason R. Mock11Division of Pulmonary Diseases and Critical Care Medicine, University of North CarolinaDivision of Pulmonary Diseases and Critical Care Medicine, University of North CarolinaDivision of Pulmonary Diseases and Critical Care Medicine, University of North CarolinaDepartment of Medicine, University of North CarolinaDepartment of Respiratory Care, University of North CarolinaDivision of Pulmonary Diseases and Critical Care Medicine, University of North CarolinaDivision of Pulmonary Diseases and Critical Care Medicine, University of North CarolinaDepartment of Medicine, University of North CarolinaDivision of Pulmonary Diseases and Critical Care Medicine, University of North CarolinaMarsico Lung Institute, University of North CarolinaDivision of Pulmonary Diseases and Critical Care Medicine, University of North CarolinaDivision of Pulmonary Diseases and Critical Care Medicine, University of North CarolinaAbstract Background Foxp3+ regulatory T cells (Tregs) play essential roles in immune homeostasis and repair of damaged lung tissue. We hypothesized that patients whose lung injury resolves quickly, as measured by time to liberation from mechanical ventilation, have a higher percentage of Tregs amongst CD4+ T cells in either airway, bronchoalveolar lavage (BAL) or peripheral blood samples. Methods We prospectively enrolled patients with ARDS requiring mechanical ventilation and collected serial samples, the first within 72 h of ARDS diagnosis (day 0) and the second 48–96 h later (day 3). We analyzed immune cell populations and cytokines in BAL, tracheal aspirates and peripheral blood, as well as cytokines in plasma, obtained at the time of bronchoscopy. The study cohort was divided into fast resolvers (FR; n = 8) and slow resolvers (SR; n = 5), based on the median number of days until first extubation for all participants (n = 13). The primary measure was the percentage of CD4+ T cells that were Tregs. Results The BAL of FR contained more Tregs than SR. This finding did not extend to Tregs in tracheal aspirates or blood. BAL Tregs expressed more of the full-length FOXP3 than a splice variant missing exon 2 compared to Tregs in simultaneously obtained peripheral blood. Conclusion Tregs are present in the bronchoalveolar space during ARDS. A greater percentage of CD4+ cells were Tregs in the BAL of FR than SR. Tregs may play a role in the resolution of ARDS, and enhancing their numbers or functions may be a therapeutic target.http://link.springer.com/article/10.1186/s12967-020-02595-3Acute respiratory distress syndromeRegulatory T cellsResolution |
| spellingShingle | Dustin L. Norton Agathe Ceppe Miriya K. Tune Matthew McCravy Thomas Devlin M. Bradley Drummond Shannon S. Carson Benjamin G. Vincent Robert S. Hagan Hong Dang Claire M. Doerschuk Jason R. Mock Bronchoalveolar Tregs are associated with duration of mechanical ventilation in acute respiratory distress syndrome Journal of Translational Medicine Acute respiratory distress syndrome Regulatory T cells Resolution |
| title | Bronchoalveolar Tregs are associated with duration of mechanical ventilation in acute respiratory distress syndrome |
| title_full | Bronchoalveolar Tregs are associated with duration of mechanical ventilation in acute respiratory distress syndrome |
| title_fullStr | Bronchoalveolar Tregs are associated with duration of mechanical ventilation in acute respiratory distress syndrome |
| title_full_unstemmed | Bronchoalveolar Tregs are associated with duration of mechanical ventilation in acute respiratory distress syndrome |
| title_short | Bronchoalveolar Tregs are associated with duration of mechanical ventilation in acute respiratory distress syndrome |
| title_sort | bronchoalveolar tregs are associated with duration of mechanical ventilation in acute respiratory distress syndrome |
| topic | Acute respiratory distress syndrome Regulatory T cells Resolution |
| url | http://link.springer.com/article/10.1186/s12967-020-02595-3 |
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