Bronchoalveolar Tregs are associated with duration of mechanical ventilation in acute respiratory distress syndrome
- PDF / 2,490,027 Bytes
- 17 Pages / 595.276 x 790.866 pts Page_size
- 2 Downloads / 162 Views
Journal of Translational Medicine Open Access
RESEARCH
Bronchoalveolar Tregs are associated with duration of mechanical ventilation in acute respiratory distress syndrome Dustin L. Norton1,2,7, Agathe Ceppe1,2,3, Miriya K. Tune1,2,3, Matthew McCravy2,8, Thomas Devlin4, M. Bradley Drummond1,2,3, Shannon S. Carson1,2,3, Benjamin G. Vincent2,5,6, Robert S. Hagan1,2,3, Hong Dang3, Claire M. Doerschuk1,2,3 and Jason R. Mock1,2,3,9*
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 C D4+ 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 C D4+ 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. Keywords: Acute respiratory distress syndrome, Regulatory T cells, Resolution Background Acute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by a marked inflammatory response within the alveolar space, resulting in rapid-onset of bilateral pulmonary infiltrates and acute *Correspondence: [email protected] 9 Division of Pulmonary Diseases and Critical Care Medicine, Department of Medicine, University of North Carolina School of Medicine, Marsico Hall 7203, 125 Mason Farm Road, Chapel Hill, NC 27599, USA Full list of author information is available at the end of the article
respiratory failure [1]. ARDS continues to account for 10% of intensive care unit (ICU) admissions, and in-hospital mortality can be as high as 46% in its most severe form [2]. Understanding mechanisms of resolution of acute lung injury (ALI) is necessary to inform interventions and improve outcomes in ARDS. Foxp3+ regulatory T-cells (Tregs) are a population of CD4+ lymphocytes shown to suppress and down-regulate immune responses [3, 4]. Tregs have esse
Data Loading...
