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 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.

Low Alveolar Macrophage Function, Low IL-6, and High CD4 Cell Count Interaction in BALF of Severe Pneumonia Patients with Extubation Success

“…38 The role of BALF CD4 + T-cells has been investigated in patients with lung injury and reported that a higher percentage of BALF CD4 + T-cells, especially Tregs, could help patients' lung injury to resolve quickly and eventually undergo extubation success. 39 Our study also reported the levels of in ammatory biomarkers for Tregs [Foxp3 + CD25+ / CD4 (%)] in the supplementary, with no signi cant difference between the groups. As the Tregs are the division of CD4 + T cells, we assumed that the levels of Tregs and the absolute CD4 + T cells would likely contribute to the extubation success and survival of the patients.…”

Low BALF CD4 T cells count is associated with extubation failure and mortality in critically ill covid-19 pneumonia

“…This study also displayed a high level of Tregs in extubation success and survived groups, albeit statistically not significant. This result indicates the vital function of Tregs as an immune suppressor in helping the adaptive immune process [ 60 ], and its role in the lung epithelial regeneration and surfactant production [ 61 ], as well as the potential effect on the resolution of the lung [ 62 ]. Future studies are required to investigate the detailed mechanisms of Tregs and the association with extubation success or extubation failure, which may better explain this present study.…”

Characterization of the MT‐2 Treg‐like cell line in the presence and absence of forkhead box P3 (FOXP3)

“…By contrast, primary Tregs express several FOXP3 isoforms in the same cell, as we and others have demonstrated previously. 28,29 Our results indicate that FOXP3 may have a role in MT-2 cell cycle progression. FOXP3-KO MT-2 cells are enriched for the G0/G1 cell cycle phase relative to WT MT-2 cells and exist in the G2/M phase in a much smaller population than WT MT-2 cells.…”

“…(d) Left: Flow cytometry plots of WT and FOXP3‐KO MT‐2 cells stained with the FOXP3 PCH101 (Exon 2 epitope) and 150D antibodies (Exon 1 epitope). Right: Schematic showing where the FOXP3 PCH101 and FOXP3 150D antibodies bind to the FOXP3 protein (adapted from Norton et al 28 …”