Bronchoalveolar Tregs are associated with duration of mechanical ventilation in acute respiratory distress syndrome

Journal of Translational Medicine

Benjamin G. Vincent¹  Matthew McCravy²  Thomas Devlin³  Agathe Ceppe⁴  Miriya K. Tune⁴  Shannon S. Carson⁴  Robert S. Hagan⁴  M. Bradley Drummond⁴  Claire M. Doerschuk⁴  Jason R. Mock⁵  Dustin L. Norton⁶  Hong Dang⁷ 

[1] Department of Medicine, University of North Carolina, Chapel Hill, NC, USA;Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA;Division of Hematology/Oncology, University of North Carolina, Chapel Hill, NC, USA;Department of Medicine, University of North Carolina, Chapel Hill, NC, USA;Division of Pulmonary, Allergy, and Critical Care Medicine, Duke University School of Medicine, Durham, NC, USA;Department of Respiratory Care, University of North Carolina, Chapel Hill, NC, USA;Division of Pulmonary Diseases and Critical Care Medicine, University of North Carolina, Chapel Hill, NC, USA;Department of Medicine, University of North Carolina, Chapel Hill, NC, USA;Marsico Lung Institute, University of North Carolina, Chapel Hill, NC, USA;Division of Pulmonary Diseases and Critical Care Medicine, University of North Carolina, Chapel Hill, NC, USA;Department of Medicine, University of North Carolina, Chapel Hill, NC, USA;Marsico Lung Institute, University of North Carolina, Chapel Hill, NC, USA;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, 27599, Chapel Hill, NC, USA;Division of Pulmonary Diseases and Critical Care Medicine, University of North Carolina, Chapel Hill, NC, USA;Department of Medicine, University of North Carolina, Chapel Hill, NC, USA;Section of Pulmonary, Critical Care, Allergy and Immunologic Diseases, Wake Forest School of Medicine, Winston-Salem, NC, USA;Marsico Lung Institute, University of North Carolina, Chapel Hill, NC, USA;

关键词: Acute respiratory distress syndrome;    Regulatory T cells;    Resolution;   

DOI  :  10.1186/s12967-020-02595-3

来源: Springer

【 摘 要 】

BackgroundFoxp3+ 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.MethodsWe 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.ResultsThe 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.ConclusionTregs 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.

【 授权许可】

CC BY